Rhesus monkeys were trained to press a lever one hundred times (FR 100) to obtain either a food pellet or an intravenous drug injection. Two daily experimental sessions, one in the morning and one in the afternoon, were divided into three 15 minute periods each. In Periods 1 and 3 lever pressing behavior was maintained by the delivery of food. Period 2 lever pressing was maintained by the intravenous injection of a drug solution. The drug available each day followed a four day sequence of cocaine (30 microgram/kg/injection), saline (1.0 ml/injection), cocaine, and test compound. This four day sequence was repeated to test a series of 16 psychoactive compounds at two doses each. These drugs were compared to saline for their ability to maintain Period 2 responding during the afternoon session. Morphine, oxymorphone, codeine, pentazocine, d-amphetamine and methylphenidate all maintained responding at rates significantly greater than for saline. Cyclazocine, naloxone, levallorphan, scopolamine, chlorpromazine, fenfluramine, and (+/-)-9-nor-9-alpha-hydroxy-hexahydrocannabinol (alpha-HHC) did not maintain responding during Period 2. The results with procaine, beta-HHC and nalorphine were considered equivocal. The authors suggest the use of a rapid substitution procedure as a method of initial screening of drugs with potential reinforcement efficacy.