Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial 201Tl SPECT (EX-Tl). EX-Tl were performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient 201Tl perfusion defects under control conditions. 201Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient Dilation Index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p < 0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of them revealed improvements of TDI and 7 of those 10 patients disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p < 0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM.