Other than the infamous Tuskegee syphilis experiments, perhaps the highest profile unethical research study ever conducted was the CIA program known as MK-ULTRA. In this series of studies, conducted in the early days of the Cold War, CIA researchers sought to discover drugs or techniques that could be used to control, or influence, subjects. They also sought new ways to extract information from interrogation subjects. One of the drugs they used was the hallucinogen LSD, which was often administered to unwitting subjects who had not given their consent (though many subjects, including Ken Kesey, famous advocate of LSD use, volunteered for the study).

In addition to the use of LSD and similar drugs, CIA researchers administered electric shock treatment and other torture techniques, again on unwitting subjects, including inmates in American prisons. At least one individual died during the experiments, a man who jumped from a window and fell to his death while under the influence (without his knowledge) of LSD. Some others claimed lasting psychological damage from experiments associated with MK-ULTRA. In the late 1970s, a Senate commission report on the program led to legislation banning such experiments, largely on the grounds that they were unethical due to the lack of consent on the part of their subjects.