Cocaine can induce serious cardiovascular sequelae, including myocardial depression and coronary artery constriction. The objective of this study was to determine, in the experimental canine model, whether the calcium channel blocker diltiazem, administered intravenously, can ameliorate cocaine-induced cardiotoxicity. The study was conducted in two parts. In the first part of the study, the protective effect of diltiazem against cocaine-induced cardiotoxicity was evaluated. Dogs given pentobarbital were pretreated with either diltiazem 0.25 mg/kg or saline, and then given a 10-mg/kg intravenous bolus of cocaine. In the second part of the study, the role of diltiazem in the treatment of cocaine-induced left ventricular myocardial dysfunction was evaluated. All dogs received a 10-mg/kg intravenous bolus of cocaine. The dogs then received either diltiazem 0.25 mg/kg intravenously or saline. Administration or diltiazem before cocaine reduced the cardiotoxic effects of cocaine. Compared with the control group, there was less depression of the first derivative of left ventricular pressure (LV dP/dt), cardiac output, and left ventricular end diastolic pressure. ST segment elevation occurred in the majority of the control animals after cocaine injection but in none of the animals pretreated with diltiazem. In the second part of the study, cocaine produced left ventricular dysfunction in all animals and ST segment elevation on the electrocardiogram in a majority of the animals. Treatment with diltiazem after the onset of cocaine-induced myocardial dysfunction did reverse the ST segment elevation. It did not, however, improve the hemodynamics significantly compared with the control group. Partial recovery of left ventricular function occurred at 15 minutes in both groups. It was concluded that, in the canine model, administration of diltiazem before injection of cocaine prevents myocardial depression and ST segment elevation. Diltiazem is also effective as treatment to reverse cocaine-induced ST segment elevation but not cocaine-induced myocardial depression.