Research has shown that many variables influence the reinforcing effects of drugs. The purpose of the present study was to compare the reinforcing effects of cocaine and the long-acting cocaine analogue 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) in rhesus monkeys during the 1st versus the last day of substitution. When PTT and cocaine were initially substituted for food or the training dose of cocaine, a large number of injections were self-administered. However, when the 1 st day of substitution was compared with the last day, the number of injections obtained with PTT but not cocaine were significantly lower. This effect was observed under different schedule conditions and in cocaine-naive and cocaine-experienced monkeys. These results suggest that when studying long-acting cocaine analogues, unlike cocaine itself, quantitative differences may be seen early in substitution testing compared with stable performance after multiple-session substitution.