Animals Used in Research

Research institutions registered under the Animal Welfare Act (AWA) are required to submit an annual report to the USDA's Animal and Plant Health Inspection Service (APHIS) that details, among other specifications, the common names and the numbers of reportable species used.

In 2024, APHIS received reports from 1,014 research facilities covering some 775,000 AWA‑regulated animals, including approximately 134,000 guinea pigs, 115,000 rabbits, 72,000 hamsters, 104,000 nonhuman primates (NHPs), 43,000 dogs, 45,000 pigs, 12,000 cats, 12,000 sheep, 63,000 birds, and 174,000 individuals of other species. The use of dogs, cats, guinea pigs, hamsters, and rabbits decreased from 2023 to 2024, while the number of NHPs used remained relatively stable (1).

In the US, there are no federal reporting requirements for mice, rats, birds, amphibians, or fish used in research, making precise numbers for these species difficult to determine. In general, these numbers are obtained from managers of in-house breeding colonies, commercial vendors, and sometimes collectors; production and sales data from the latter two are proprietary and not disclosed publicly.

In 2023, research oversight and animal welfare organizations estimated that 25–30 million mice and rats are used for research annually in the US. More than 95% of all research animals (2, 3), along with 4–5 million zebrafish (4) and > 100,000 amphibians (5), are used in genetic, developmental, and environmental studies.

Sequencing human and animal genomes has led to precision medicine that aims to tailor treatments for individuals on the basis of genetics, environment, and lifestyle, rather than generalizing therapy for the population. Proof-of-precision studies and studies based on animal models indicate the need for a broader diversity of species and genotypes beyond conventional mouse-centric models. Since 2023, precision medicine has increasingly used comparative genomics and multispecies models (including rats, zebrafish, dogs, pigs, and NHPs) to study genetic variation.

In 2024, NIH-supported consortia and European programs like Infrafrontier emphasized using genetically diverse resources such as Diversity Outbred (DO) and Collaborative Cross (CC) mice or patient-derived xenografts (human cancer cells embedded in immunodeficient rodents). These better represent differences in human disease pathogenesis and therapeutic response. These efforts aim to decrease translational failure and enhance predictive value and validity by reflecting human population heterogeneity.

The domestic mouse, Mus musculus, is a popular research model because of its small size, short lifespan, adaptability, docility, low cost, fecundity, and defined health and genetics. Genetic manipulation, such as with human and other animal genes, tumors, immune cells, or microbiome components, is also relatively easy in mice.

Embryonic genome editing techniques, such as CRISPR (clustered regularly interspaced short palindromic repeats) and prime editing, have greatly improved the use of genetically engineered mice in research. This has led to establishment of numerous mutant mouse genotypes with immune defects and inherited diseases similar to those of humans and other mammals. Base and epigenome editing have enabled the development of mice with precise single-nucleotide modifications and targeted gene expression regulation.

Phenotyping and single-cell multiomics (eg, transcriptomics, epigenomics, proteomics) have enhanced functional characterization and decreased the time from bench to bedside. Mouse models now coengraft multiple human tissue systems, enhancing their utility in infectious disease and oncology research.

The domestic Norway rat (Rattus norvegicus) is the second most common rodent, after the mouse, used in research. Rats share many of the desired research attributes of mice, and their larger size makes them better suited for surgical manipulations and behavioral studies. Mutant, inbred, and outbred rat strains are used in studies on aging, cancer, drug effects, addiction, arthritis, brain injury, hypertension, embryology, endocrine diseases, neurophysiology, infectious diseases, stroke, organ transplantation, and surgically induced disease.

CRISPR and base editing advancements have enabled transgenic rat models for Alzheimer disease, retinal degeneration, and metabolic syndromes. Rats are favored over mice in neurobehavioral and immune system studies because of their larger brains and better suitability for imaging.

Guinea pigs and rabbits are the most common research mammals after mice and rats; however, their numbers in research settings have declined since the 1990s. 

The guinea pig (Cavia porcellus) was among the first animals used in biomedical research. Guinea pigs are used in research on respiratory virology and tuberculosis because their airway physiology is similar to that of humans. They also contribute substantially to research in immunology, vaccines, and hearing. However, their overall use in research has declined because of their long gestation (59–72 days) and small litter size (2–5).

The use of rabbits in product safety testing has declined. However, rabbits are vital for research on ocular drug delivery, atherosclerosis, and tissue engineering. In addition, interest in transgenic rabbit lines for studies of immunology and therapeutic antibodies is aided by CRISPR advances.

Hamsters are used to study obesity, carcinogenesis, prostatic disease, toxicoses, infectious diseases (including slow viruses), dental caries, chronic bronchitis, and teratogenesis. Syrian and Siberian hamsters are key models for COVID-19 research because of their susceptibility to SARS-CoV-2, enabling studies of viral pathogenesis, transmission, and vaccine or antiviral efficacy. 

Besides the Syrian hamster (Mesocricetus auratus), other hamster species used in research include Armenian, Siberian (dwarf or Djungarian), Chinese, European, and Turkish hamsters. Hamsters are readily available, reproduce easily, and are mostly disease-free; however, they are susceptible to induced viral diseases.

Other rodent species used in research include gerbils, deer mice, chinchillas, cotton rats, rice rats, multimammate rats, spiny mice, degus, voles, and woodchucks.

Although rodent models are the most commonly used mammals in research, larger animals like dogs offer unique opportunities in biomedical research, especially for studies on cardiovascular disease, endocrinology, orthopedic disorders, and pharmacokinetics. Their size, trainability, and physiology make dogs suitable for surgical models and prosthetic device testing. Dogs are vital in translational research, particularly for chronic implantation and telemetry. Purpose-bred beagles are commonly used for their docile temperament and uniform size. 

The use of dogs in research has declined since 1984, while the use of several livestock species has increased. This shift is a consequence of regulatory and public pressure regarding dog use; however, it is also due to the comparative anatomy and physiology of livestock, which make them better models for certain investigations. For example, swine are used in cardiovascular research, digestive physiology studies, as surgical models, and for xenotransplantation. Sheep are used to study neonatal development, human vaccine improvement, asthma, drug delivery, circadian rhythms, and surgical techniques.

Nonhuman primates are vital for vision, neuroscience, infectious disease, vaccine, and safety testing studies. They have become valuable models of HIV infection and age-related neurodegenerative diseases. Regulatory scrutiny of research conducted on NHPs has led nations like the Netherlands and Canada to tighten ethical review and restrict funding for NHP research without exceptional justification.

Chimpanzees (Pan troglodytes) have been prohibited from US biomedical research since 2015, and most have been retired to sanctuaries worldwide. Supply chain limits, conservation issues, and macaque export bans from Asia have driven the development of alternative research models, such as marmosets and transgenic rodents, and intensified the refinement of existing macaque colonies.

The use of cats in research has declined since 1980. However, cats remain important models in studies of neuroscience, aging, inherited diseases, and infectious diseases. Cats infected with feline immunodeficiency virus are used for studies of translational neurology, particularly epilepsy, spinal cord injury, and lentiviral pathogenesis.

Key aquatic research species are zebrafish (Danio rerio), tetraploid South African clawed frogs (Xenopus laevis), and diploid, fast-maturing Xenopus tropicalis from West Africa. Zebrafish are easily mutated for disease and cancer research. Clawed frogs are valuable for studying the cell cycle and gene function. 

High-throughput CRISPR mutagenesis and automated imaging have enhanced zebrafish applications in toxicology, rare disease gene discovery, and neurobehavioral phenotyping. Xenopus spp are increasingly used in functional genomics and regenerative biology with single-cell multiomics and CRISPR.

Other species used in research include goats, calves, horses, ferrets, armadillos, opossums, birds, reptiles, other amphibians, other fish species, and invertebrates. At the time of this writing, ferrets are the leading small animal model for influenza and SARS-CoV-2 variant research. Invertebrates like fruit flies, roundworms, and cephalopods are advancing as research subjects in neurobiology and behavioral science because of improved genetic tools and imaging technology.