Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in rodent brain. Additionally, local anesthetics are self-administered in rhesus monkeys. The present study determined binding affinities of cocaine and five local anesthetics at dopamine transporters in rhesus monkey brain, and compared binding affinities to published self-administration potencies in rhesus monkeys. The affinity order at dopamine transporters was cocaine > dimethocaine > tetracaine > procaine > or = chloroprocaine > lidocaine. The correlation between dopamine transporter affinities and self-administration potencies was significant. Binding affinities were also determined at sodium (Na2+) channels in rhesus monkey brain. There was not a significant correlation between Na2+ channel affinities and self-administration potencies Local anesthetics with high dopamine transporter and low Na2+ channel affinities were self-administered, whereas those with either high or low affinity at both sites were not consistently self-administered. These data suggest that affinity at dopamine transporters is related to the reinforcing effects of local anesthetics in rhesus monkeys, and Na2+ channel effects may interfere with the reinforcing effect of these drugs.