Four monkeys (Cercopithecus aethiops) were trained to discriminate 0.06 mg/kg of lysergic acid diethylamide (LSD) from saline in a two-key task in which correct responding was reinforced with food under a fixed ratio 32 schedule. The ED50 of LSD was 0.011 mg/kg. The nonhallucinogenic ergot, lisuride, and the hallucinogen, 5-methoxy-N,N-dimethyltryptamine, substituted completely for LSD (ED50 values were 0.0098 and 0.45 mg/kg, respectively). Mescaline (1-40 mg/kg), d-amphetamine (0.1-0.625 mg/kg) and apomorphine (0.1-0.5 mg/kg) did not substitute for LSD. In antagonism testing with ketanserin (1-10 mg/kg) or pirenperone (0.025 and 0.05 mg/kg), only the highest dose of pirenperone attenuated the LSD stimulus effect (to 55%). A 0.1-mg/kg dose of pirenperone produced nonresponding in three of four animals. The LSD cue was unaffected by clozapine (1 and 2 mg/kg), haloperidol (0.1 mg/kg) and pizotifen (0.6-1.8 mg/kg). The fact that lisuride does not readily cause hallucinations in humans, but yet substituted for LSD in primates, indicates that the LSD cue may not reflect the hallucinogenic properties of LSD. It is suggested that the LSD stimulus effect may depend on receptors (e.g., serotonergic) that, at the moment, are only poorly characterized.