Following trials in Japan, Nicorandil (SG-75) has been introduced as a new antianginal drug with coronary dilatory properties. The effects of 20 mg SG-75 administered sublingually were studied in 9 patients with coronary artery disease and reproducible pacing-induced myocardial ischemia (MIS) (rise in left ventricular enddiastolic pressure, changes in ST-segment, and angina). Changes in heart rate, arterial pressure and angiographic left ventricular ejection parameters, contractility, parameters derived from left ventricular function (ejection fraction, cardiac index, stroke work index) and cardiac work (left ventricular stroke work index, left ventricular work), myocardial oxygen consumption, cardiac efficiency (LVeff), and regional wall motion (RWM) were investigated for the following hemodynamic phases: 7th and 14th minute after SG-75, the immediate postpacing phase without medication (PPP), and the postpacing phase under the influence of SG-75 (PPP + SG). In the 7th and 14th minute after SG-75 and in the absence of stress, there was no variation from control values (p less than 0.05). In the 15th and 16th minute after SG-75 (serum-level control), under pacing stress equivalent to that measured in the PPP, the MIS observed in the absence of medication did not now occur. Moreover, in the PPP + SG-75 phase the following mean parameter changes were noted: ejection fraction +21%, cardiac index +37%, left ventricular stroke work index +48%, left ventricular work +52%, and LVeff +60%; RWM also improved. Prophylaxis of ischemia and improved hemodynamics under the influence of SG-75 were probably due to a decrease in preload (left ventricular enddiastolic pressure -41%) and afterload (stroke volume ratio -29%). Similar changes might have been expected after nitroglycerin, if given under equivalent conditions. Since no harmful effects, either subjective or objective, were apparent during or after application of SG-75, this seems to be a promising drug for the antianginal therapy of the future.