The effects of slow-release isosorbide-5-mononitrate (IS-5-MN), 25 mg once daily, bupranolol, 50 mg once daily, and their combination on exercise-induced ST-segment depression at comparable work load, maximal work load, exercise capacity, frequency of anginal episodes and sublingual nitroglycerin consumption were studied in 30 patients with chronic stable angina pectoris. The patients were assigned in a randomized, double blind protocol, to either form of monotherapy, for 12 days, and thereafter to combined therapy for 12 days. Exercise stress test was performed before treatment and at 2 and 16 h after drug administration on the first and 12th day of each treatment period. ST-depression at comparative work load at 2 h after dosing was reduced by 49% acutely after administration of IS-5-MN. This effect was not significantly altered after 12 days of treatment and during combined therapy. In those patients treated by bupranolol alone, an effect was observed only after 12 days – a 24% reduction in ST depression. At the 12th day of combined therapy ST-segment depression was reduced by 65%. At 16 h after dosing there was no significant reduction in mean values of ST-segment depression in either groups, but some patients in each group showed a sustained effect for 16 h. Both drugs increased maximal work load and exercise capacity at 2 h after administration. This effect was sustained in the IS-5-MN group also at 16 h after administration. In the bupranolol group only the increase in exercise capacity was sustained for 16 h after administration. Combined therapy has only slightly improved the effect of monotherapy. The frequency of anginal episodes and sublingual nitroglycerin consumption were reduced with both forms of monotherapy, but more with IS-5-MN. Combined therapy increased the effect of bupranolol but not of IS-5-MN. In conclusion, sustained-release IS-5-MN exerts a significant increase in exercise tolerance for at least 16 h after dosing, in monotherapy as well as in combined therapy with beta-blocker. The efficacy during the prolonged therapy over 12 days was without attenuation.