The response to nimodipine as an inhibitor of cocaine toxicity was investigated in pentobarbital-anesthetized dogs and in isolated dog heart preparations at constant heart rates. Nimodipine (10 micrograms/kg) markedly decreased peripheral and coronary vascular resistance and increased cardiac output, cardiac work, and coronary blood flow. When corrected for the change in afterload, nimodipine had a positive inotropic response, as measured by +/- maximal dP/dt, in the cocaine-depressed animal. Thus, cocaine toxicity was partially reversed by nimodipine. In the isolated heart preparation, nimodipine resulted in further cardiac depression similar to that seen with other calcium channel antagonists.