214 patients with angina pectoris were randomized to placebo or isosor-bide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed. Conclusion: ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.