The use of animals in experimentation dates back to the ancient Greeks and Romans. In the late 16th and early 17th centuries, the scientific revolution began. During the 18th and 19th centuries the use of animals in experimentation slowly progressed from a relatively uncommon practice into the scientific mainstream. In the mid-1800s, principles for regulating animal research were proposed in Great Britain (Rowan, 1984a), and, in the late 1800s, there was a surge in antivivisectionist activity throughout Europe and in the United States.

A variety of social forces influenced the growth of this sentiment in Europe (French, 1975; Rupke, 1987; Turner, 1980). These forces included Jeremy Bentham's late 18th-century utilitarian arguments about the moral significance of animal suffering and the impact of Charles Darwin's On the Origin of Species on prevailing attitudes regarding the status of humans and animals. Darwin's theory challenged the anthropocentric view of nature that placed human beings at the teleological center of the universe. The social elite began to question how animals were treated, especially in research laboratories. The same social forces were at work in America, and the practice of animal research and opposition to it began to grow in the late 1800s. There were unsuccessful attempts in the United States to pass legislation similar to the animal-research controls passed in 1876 in Great Britain. Throughout the 1890s, bills were introduced in the U.S. Congress to regulate the use of animals in research in the District of Columbia (then a hub of medical research in America). One of these bills, the Gallinger Bill, was even endorsed by six Supreme Court justices and many other eminent professionals in Washington.

By the end of the First World War, animal-protection issues were claiming much less public attention, and the movement entered its second phase in which most humane organizations were content to promote humane education and enforce animal-cruelty laws. The American Society for the Prevention of Cruelty to Animals (ASPCA) withdrew its opposition to animal research and passed what amounted to a vote of confidence in the medical profession's concern for animals.

The third phase of opposition began in 1950 and continues unabated to the present. Organizations like the Animal Welfare Institute (1951) and The Humane Society of the United States (1954) were founded to devote attention to the animal research issue. Initially, these groups focused on the care of laboratory animals. Eventually, in 1966, the U.S. Congress took action and passed the Laboratory Animal Welfare Act. This original legislation, prompted in part by a Life magazine exposé on the conditions at an animal dealer's facility, regulated only the acquisition and handling of animals by dealers. It was amended in 1970 (and the name shortened to the Animal Welfare Act) to include the care of animals in research institutions. However, birds, rats and mice, which account for about 85% of all laboratory animals, were excluded from regulatory oversight by order of the Secretary of Agriculture and remain outside U.S. Department of Agriculture oversight—but not the guidelines produced by the Public Health Service—even today.

Pressure continued to be applied on both federal and state legislatures to tighten the laws controlling animal research. Several states either repealed laws permitting the release of pound animals to research institutions or abolished the practice altogether. At the federal level, two scandals involving animal research, in 1981 and 1984, led to a public clamor for more regulation, and new legislation was passed by the U.S. Congress in 1985. One of the bills required the National Institutes of Health to upgrade its animal research oversight, and the other amended the Animal Welfare Act to require more attention to protocol review (in-house scrutiny of proposals for laboratory animal use) and the reduction of animal pain and distress in laboratories.

Legislative battles have continued into the 1990s over mandated release of shelter animals to laboratories, product safety testing, protection of research facilities against break-ins and vandalism, the treatment of nonhuman primates, whether research should be covered under state animal cruelty laws, and student rights regarding dissection and animal experimentation. Since 1987, for example, approximately one quarter of the states have seen the introduction of bills to restrict the use of animals for educational purposes. In 1998, federal legislative proposals on the retirement of research chimpanzees and the regulatory acceptance of alternative testing methods reflect a more bipartisan approach to reform.