The influx of calcium ions into the myocardial cell sets in motion a series of steps which end with contraction. Reduced intracellular calcium activity diminishes the contractile and mechanical function and thereby lowers myocardial oxygen demand. This is a beneficial effect when the myocardium is threatened by ischemia, such as occurs during transient coronary occlusion. We investigated the direct intracoronary injection of nifedipine, a known Ca2+ antagonist, immediately prior to transluminal angioplasty (PTCA). It was reasoned that the specific inhibitory action of nifedipine on contractile energy expenditure could provide temporary support for ischemic or potentially ischemic cardiac cells in that region during such induced interruption of flow. In order to test this hypothesis, the hemodynamic response was measured in 11 patients, first, to the injection of 0·2 mg nifedipine in the left main coronary artery, and second, to the transluminal occlusion of the stenosis for 45 s during PTCA. A second group of 14 patients was also studied for lactate production before and after PTCA of the left anterior descending artery (LAD) either with or without superselective intracoronary injection of nifedipine distal to the stenosis in the LAD. Coronary sinus (CSF) and great cardiac vein flow (GC yE), difference in lactate (A-GCV) and left ventricular isovolumic contraction (peak+/dP/dt, Vmax) were monitored. A 45 occlusion of LAD virtually eliminates all flow and induces severe ischemia accompanied by impairment of LV contractility and relaxation. Nifedipine i.c., while reducing the contractile and mechanical function of the anterior wall by a regional cardioplegic effect, increases the poststenotic flow. Lactate production in the great cardiac vein following (15 s) the LAD occlusion (TO) rose sharply. Such release is almost completely suppressed when transluminal occlusion was performed immediately after the i.c. administration of nifedipine (02 mg). It is postulated that the specific inhibitory action of nifedipine on contractile energy expenditure prevents ischemic cardiac cells from becoming anaerobic, during transluminal occlusion for periods lasting up to 90s. This may prevent them from acquiring damage, as a result of what otherwise must be termed a potentially beneficial procedure.