The purpose of the study was to assess the ability of the calcium channel blocker diltiazem to limit infarct size in rat. Myocardial infarct size was measured by planimetry of histologic sections of serial slices of ventricular mass 48 h after left coronary artery ligation. Each section was stained for succinic dehydrogenase activity. Diltiazem was used as an intravenous infusion (30 or 100 μg.kg −1.min −1) given for 20 min before and 60 min after ligation. Diltiazem-treated hearts showed a significant reduction in the volume of necrotic myocardium. However, the topography of the protection was complex. In diltiazem-treated hearts, the extent of apical necrosis was generally greater than in untreated hearts, whereas the larger degree of protection was constantly observed at the basal level. Mean arterial blood pressure and heart rate were significantly lower in diltiazem-treated rats. On the other hand, 48 h after coronary artery ligation diltiazem-treated rats maintained significantly higher cardiac contents of ATP and creatine phosphate than did untreated rats. Such a beneficial effect of diltiazem is probably related to its ability to limit calcium overloading which usually develops during ischemia and/or to its hemodynamic action which reduces cardiac work.