Animals trained to discriminate classical hallucinogens from saline have been used in the past decade to examine other hallucinogenic agents. Time course (onset, duration of action) and locus of action have been studied, SARs have been formulated, and mechanism of action has been investigated in detail. On the basis of DD studies in animals, it was proposed that hallucinogenic agents may produce their actions in humans via a 5-HT2 agonist mechanism and that certain phenalkylamine hallucinogens such as DOM and DOB might constitute the first known examples of 5-HT2 agonists. This led to the development of [3]HDOB and [125I]DOI for use in radioligand binding and autoradiographic studies and to the use of hallucinogen-trained animals as a functional behavioral model of 5-HT2 receptor activation. Animals trained to classical hallucinogens are more recently being used to evaluate novel designer drugs. It can be seen, then, that this paradigm, using hallucinogenic agents as training drugs, has proven to be quite useful for the investigation of hallucinogens and nonhallucinogens alike.