The effect of isradipine, a dihydropyridine calcium antagonist, on cocaine intravenous self-administration in rats was investigated. Administration of (+/-)isradipine (1.25-5 mg/kg SC) 2 h before the cocaine self-administration session induced a significant and dose-dependent increase in the number of cocaine injections with respect to basal values. This effect was stereospecific, with the (+) form of isradipine being active, while the (-) stereoisomer was ineffective. These results suggest that isradipine antagonizes the rewarding properties of cocaine, possibly by inhibiting those dopaminergic systems related to reward mechanisms. These results further indicate a possible use of isradipine, or structurally similar compounds, in the treatment of cocaine related disorders.