Diltiazem is a calcium antagonist with demonstrated experimental cardioprotective effects. Its effects on myocardial infarct size were studied in 34 patients admitted within 6 hours after the first symptoms of acute myocardial infarction. These patients were randomized, double-blind to placebo or diltiazem (10-mg intravenous bolus followed by 15 mg/hr intravenous infusion during 72 hours, followed by 4 X 60 mg during 21 days). Myocardial infarct size was assessed by plasma creatine kinase and creatine kinase-MB indexes, perfusion defect scores using single-photon emission computed tomography with thallium-201 and left ventricular ejection fraction measured by radionuclide angiography. Tomographic and angiographic scanning was performed serially before randomization, after 48 hours and 21 days later. Groups were comparable in terms of age, sex, inclusion time and baseline infarct location and size. Results showed no difference in creatine kinase and creatine kinase-MB data between controls and treated patients, a significant decrease in the perfusion defect scores in the diltiazem group (+0.1 +/- 3.0 placebo vs -2.2 +/- 1.9 diltiazem, p less than 0.02) and a better ejection fraction recovery in the diltiazem group (-4.2 +/- 7.4 placebo vs +7.7 +/- 11.2 diltiazem, p less than 0.05). Myocardial infarct size estimates from perfusion defect scores and enzyme data were closely correlated. These preliminary results suggest that diltiazem may reduce ischemic injury in acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)