Rhesus monkeys, previously trained to avoid electric shock, pressed a lever to extinguish a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the onset of the light. Each response when the light was on terminated the light for a 1-minute time-out period (avoidance); a response during the infusion terminated the infusion (escape). Under these conditions the monkeys tolerated a high number of saline infusions. Saline was replaced by different doses of chlorpromazine, lysergic acid diethylamide (LSD) and pentobarbital each for six successive daily 2-hour sessions. Infusions of chlorpromazine (5.0-20 mug/kg/infusion) or LSD (1.0-2.5 mug/kg/infusion) generated and maintained avoidance/escape behavior, whereas most of the infusions of pentobarbital (10-100 mu/kg/infusion) were tolerated. In rhesus monkeys with no previous drug experience, chlorpromazine and LSD, but not pentobartital, have negative reinforcing properties.