The effectiveness and duration of the antianginal action of 20 mg isosorbide-5-mononitrate (IS-5-MN) and 20 mg of a sustained-release preparation of isosorbide dinitrate (ISDN) was assessed by serial exercise testing in 12 patients with stable effort angina. The study was double-blind, cross-over and placebo-controlled. Exercise testing was symptom-limited and was performed 4 times daily on 3 consecutive days using the Bruce protocol. The first test was performed before treatment and the remaining 1, 4 and 8 h after administration of the active drug or placebo. The time for 1 mm ST depression and for the onset of angina was delayed for 155 ± 79 (p < 0.002) and 114 ± 65 s (p < 0.002), 1 h after the administration of IS-5-MN, respectively. After 4 h, both drugs significantly prolonged the time for 1 mm ST depression and for the onset of angina: ISDN for 96 ± 75 (p < 0.009) and 84 ± 72 s (p < 0.01) and IS-5-MN for 109 ± 42 (p < 0.004) and 87 ± 53 s (p < 0.003). After 8 h, neither active drug showed any significant effect. Only IS-5-MN decreased the amount of ST segment depression (corrected by exercise time) versus placebo at 1 h test (0.24 ± 0.2 vs. 0.46 ± 0.3 s, p < 0.005) and at 4 h test (0.27 ± 0.2 vs. 0.39 ± 0.2 s, p < 0.05). It is concluded that the anti-ischemic effects of IS-5-MN are slightly more potent and are reached earlier than a sustainedrelease preparation