It has been suggested that histamine is involved in the pathogenesis of coronary spasm but its exact role remains unclear. H 1 receptor stimulation of the coronary artery was performed with a selective intracoronary infusion of histamine (2 µg/min) in 21 patients with variant angina after blockade of the H 2 receptor with Cimetidine (25 mg/kg) and its effect on the coronary artery diameter was examined. Intracoronary injection of acetylcholine was also performed in 19 of the 21 patients. Ergonovine (0.2 mg) was intravenously administered in one patient. The coronary artery diameter was measured with cinevideodensitometric analysis. A mean plasma histamine concentration in the coronary sinus increased from 4 × 10 −9 to 7 × 10 −8 M 5 min after histamine infusion into the left coronary artery (n = 18). Coronary spasm was induced in 6 patients (29%) with histamine, in 18 (95%) with acetylcholine and in 1 with ergonovine. The effect of histamine on the luminal diameter was analyzed at the site of spasm in the 26 coronary arteries in which spasm was induced by acetylcholine or ergonovine. Of the 20 coronary arteries with a normal arteriogram or a fixed stenosis ≤50% of luminal diameter, histamine decreased the diameter in 4, increased it in 14 (70%) and caused no change in 2; of the 6 coronary arteries with a fixed stenosis ≥75%, histamine decreased the diameter in 5 and increased it in 1. In the coronary arteries in which spasm was not induced by either acetylcholine or ergonovine, histamine increased the diameter, especially in those without advanced atherosclerosis. It is concluded that histamine induces coronary spasm in some patients with variant angina by stimulation of the H 1, receptor of the coronary artery and it causes coronary vasodilation in the majority of patients, especially those without advanced coronary artery disease, presumably through release of the endothelium-derived relaxing factor.