In a prospective single-blind study we examined the effects of additional molsidomine in 20 patients (63 + 10 years; 15 males, 5 females} with unstable resting angina (> 3 attacks/24 hours} refractory to triple therapy (nitrates, calcium antagonists, and beta blockers) combined with heparin or aspirin. All but one patient had coronary artery disease documented by coronarography (n = 17} or by recent myocardial infarction (n = 3). Two patients had angiographically documented severe coronary spasms. Patients entered the study if coronary bypass surgery or PTCA could not be performed within 3 days after angiography (n = 9} or was not feasible due to anatomical or technical reasons (n = 6}, concomitant malignant disease (n = 2}, or age greater than 75 years (n = 3). All patients received molsidomine orally 12 to 24 mg/day. In 15 of the 20 patients molsidomine was given i.v. initially, starting with 20 mg i.v., followed by infusion of I to 4 mg/hour. Heart rate and blood pressure did not change significantly, and eight patients had a slight decrease of systolic and diastolic blood pressure. Severe adverse effects did not occur, and moderate headaches were reported by five patients. In 13 patients, unstable angina could be stabilized, and they remained free of resting angina; five had a marked reduction of the frequency of anginal attacks. In two patients, molsidomine was without demonstrable beneficial effects. After a follow-up of 4 weeks, nine patients were free of symptoms after bypass surgery or PTCA, 10 continued to have angina NYHA class II or III, and one patient died due to acute myocardial infarction and cardiogenic shock 4 days after starting additional molsidomine. We conclude that molsidomine is well tolerated and has a marked beneficial effect in patients with refractory unstable angina. Molsidomine should therefore be considered for routine therapy of unstable angina, especially in those patients who are suspected of tolerance to nitrate therapy.