The purpose of the present study is to assess the effect of nicorandil, a coronary vasodilator with a mechanism of potassium channel opening, on the abnormal myocardial Tl-201 perfusion evoked by exercise. Eleven patients who had a history of typical angina, positive exercise electrocardiograms, positive Tl-201 scintigraphy, nearly normal coronary arteriograms, and negative coronary vasospasm underwent exercise Tl-201 scintigraphies under no medication (baseline test) and administration of nicorandil (nicorandil test). Tl-201 was injected at a matched workload in both tests. Nicorandil did not alter heart rate, blood pressure, or the Methods rate-pressure product at the end of the exercise, but it significantly improved the extent score from 0.37 +/- 0.22 to 0.20 +/- 0.15 (p < 0.05) and the severity score from 33.9 +/- 32.2 to 13.5 +/- 16.4 (p < 0.05), and also significantly hastened the Tl-201 mean washout rate from 30.5 +/- 14.8% to 37.4 +/- 13.1% (p < 0.05). Anginal symptoms disappeared in 3 of 5 cases and ST depression improved in 5 of 7 cases after nicorandil. We conclude that nicorandil augments coronary flow reserve, possibly due to a reduction of vasotone in the small coronary arteries.