A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants. A slow onset of action has been hypothesized to weaken the reinforcing effects of drugs. The present study evaluated this hypothesis with slow-onset cocaine analogs, WIN 35428, RTI 31, and RTI51. When cocaine or a cocaine analog was made available to rhesus monkeys (n = 4 or 5) for self-administration under a progressive-ratio (PR) schedule with a 1-h time-out between injections, all the drugs functioned as positive reinforcers. The maximum number of injections was in the order of cocaine > WIN 35428 > RTI 31 > RTI51. In in vivo binding in rat striatum, equipotent doses of cocaine, WIN 35428, RTI 31, and RTI51 were estimated to displace 25% of [(3)H]WIN 35428