To evaluate the protective effect of nifedipine on ischemic myocardium, in addition to thrombolytic therapy, a total of 149 patients with acute myocardial infarction were included in a double-blind controlled study in which they received 20 mg sublingual nifedipine (74 patients in group 1) or placebo (75 patients in group 2) in the emergency ward, either intracoronary nifedipine, 0.2 mg before and 0.2 mg after reperfusion of the infarct-related vessel and 20 mg three times/day during the hospital stay, or placebo. Combined intravenous and intracoronary thrombolytic therapy was initiated by means of mechanical recanalization in nonreperfused vessels. There were no differences between group 1 and 2 with regard to age, sex, body weight, or location of infarct. Evolution of CK-MB release and cumulative CK-MB was higher in group 1 than in group 2. Changes with regard to regional and global left ventricular function and coronary anatomy were not significantly different (NS) between the two groups. Reocclusion occurred in 15 of 74 (20%) and 10 of 75 (13%) patients in groups 1 and 2, respectively. During the reperfusion period, second- and third-degree atrioventricular block occurred in 5.4% and 6.7% (NS), ventricular couplets in 17.6% and 24% (NS), ventricular tachycardia in 2.7% and 9.3%, and ventricular fibrillation in 2.7% and 8% of the patients, respectively. Mortality rates were 13% and 8%. The study demonstrates that even very early administration of nifedipine combined with intracoronary administration does not enhance the salvage of ischemic myocardium achieved by reperfusion.