For almost thirty years, the U.S. government has required research institutions to comply with certain standards of humane animal experimentation. The two main mechanisms for setting standards have been the Animal Welfare Act enforced by the U.S. Department of Agriculture (through APHIS—the Animal and Plant Health Inspection Service) and Public Health Service initiatives (mainly through the NIH).

The Animal Welfare Act, originally enacted in 1966 and amended several times since, was passed to ensure "the humane care and treatment of laboratory animals, and the prevention of pet theft for sale to research facilities" (Morrison, 1984). The 1966 Act was very limited. It applied mainly to the acquisition, handling and sale of dogs and cats to research institutions and had relatively little impact on the care or use of animals in research laboratories. The Act's reach was extended in the 1970 amendments to include other groups of animals (but the Secretary of Agriculture excluded rats and mice), and their care in the laboratory. In addition, animals had to be given adequate anesthesia and analgesia unless such use would compromise the research. Decisions about how animals were to be used still remained largely up to individual investigators.

The 1985 amendments to the Animal Welfare Act extended its reach still further and required all registered institutions to establish Institutional Animal Care and Use Committees (IACUCs) that would not only oversee animal care but that would also, for the first time in the USA, begin to examine laboratory animal use. As the Act is now being enforced, the IACUC must pay particular attention to the question of whether or not alternatives might be available for those protocols that have the potential to cause animal pain and distress, even if the pain and distress is alleviated by drugs. Thus, the availability of possible alternatives should be considered in about 42% of the research animal use reported to the USDA (the percentages may be lower for research involving rats and mice).

The 1985 amendments also added several phrases that have begun to change housing standards for laboratory animals. Institutions were required to provide exercise for dogs and develop facilities that would promote the "psychological well-being of primates." Research facilities are now increasingly keeping primates in groups, providing "toys" and encouraging the animals to "forage" for food. These ideas are beginning to percolate down to affect ideas about housing and care for the more common laboratory species like rabbits, rats and mice.

The National Institutes of Health (NIH), part of the Public Health Service (PHS), is the major U.S. government agency funding laboratory animal research (providing about half the funding for biomedical research in the country). It has traditionally been the lead federal agency for the establishment of policies on animal experimentation. These policies originally dealt mainly with the care and maintenance of laboratory animals and not with the experimental methods themselves. This situation changed with revisions to PHS policies in 1985 in the wake of several incidents of laboratory animal abuse that were widely publicized by animal activists.

The PHS turned to its oversight of human research for a model that could be applied to animal research. Thus, all institutions receiving NIH funds had to file an assurance statement with NIH and had to either revamp existing animal care committees, or establish such committees where they did not exist, to review protocols and apply the revised PHS policies. The NIH also conducted spot checks to ensure that their standards were being maintained. For example, Columbia University, a major research institution, had its NIH funding suspended when NIH determined that its facilities and program were not up to standard.

The application of the new IACUC structure has substantially changed the way animal research projects are conceived and approved. However, the system is still relatively new and the participants are still negotiating their way through the ambiguities and uncertainties of the regulatory structure. For example, there is a considerable range of opinion over the role the local committees should play in addressing the scientific merit of proposed projects. Some argue that the committees have to become involved in the planning of the scientific research because bad science is a waste of animal resources (and also bad for the animals). Others hold that the Animal Welfare Act forbids interference in the actual conduct of research and, hence, the committees are not permitted to question the science. Animal protection organizations are not satisfied that the IACUCs have sufficient outside input from local citizens and those actively involved in animal welfare.

Recent animal protection efforts to enhance the Animal Welfare Act regulations include legal challenges to the exclusion of birds, rats and mice from regulatory coverage, recommendations to revamp the USDA's pain classification system, and calls to issue specific regulations for farm animal use in biomedical settings.