1. The present study was designed to test the hypotheses whether platelet degranulation across the coronary bed is detectable during non-ischaemic periods in patients with vasospastic angina (VSA) and whether the exogenous nitric oxide (NO) donor nitroglycerin (GTN) is able to modify platelet degranulation, reflecting an impaired endothelial production of NO. 2. We studied 13 patients with VSA and 10 controls. The time course of coronary sinus (CS) plasma 5-hydroxytryptamine (5-HT) levels was evaluated every 4 h before and after intravenous infusion of GTN over a period of 40 h. Coronary sinus plasma 5-HT levels were significantly higher at any measured time point in patients with VSA compared with control and were significantly decreased in patients with VSA following treatment with GTN, but not in controls. Femoral artery plasma 5-HT levels remained almost constant throughout the study. The ratio of CS:aorta 6-keto-prostaglandin F1 alpha was significantly and inversely correlated with the transcardiac plasma 5-HT difference only in patients with VSA (r = -0.68; P < 0.02; n = 13). 3. The time course of CS 5-HT levels confirmed significant platelet degranulation across the coronary bed supplied by the spasming artery in patients with VSA and this was modified by GTN. The present data suggest that platelet degranulation occurs during non-ischaemic periods in patients with VSA and that prostacyclin biosynthesis may be a compensatory response to an impaired endothelial release of NO, limiting the degree of the effects of platelet degranulation.