In rat striatal membranes, NaCl induced a twofold increase in the maximal number of cocaine binding sites but did not alter the affinity of these sites for cocaine. This effect was concentration-dependent, specific to sodium ions, and occurred in membranes prepared from corpus striatum but not from other brain regions. Lesions with 6-hydroxydopamine but not with kainic acid eliminated the sodium-induced increase in binding and produced a decrease in the Bmax of binding measured in the presence of NaCl. The capacity of a series of drugs to interfere with Na+-dependent cocaine binding correlated well with their capacity to inhibit [3H]dopamine uptake into rat striatal synaptosomes. The present results suggest that Na+-dependent cocaine binding sites are localized presynaptically on dopaminergic nerve terminals in corpus striatum, and may be related to dopamine uptake sites.