ABSTRACTWe evaluated the effects of selective activation of H, receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (>70% stenosis) coronary artery disease and one with normal coronaries. Selective H, receptor stimulation was achieved by infusing 0.5,ug/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 5 to 77 4 mm Hg (mean + SEM, p < .001), coronary vascular resistance (CVR) decreased from 1.07 0.17 to 0.82 + 0. 14 mm Hg/ml/min (p < .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels. In a considerable percentage of patients with vasospastic angina with or without coronary artery disease, however, H1 receptor-induced vasoconstriction of large capacitance coronary arteries may prevail over peripheral vasodilatation. These findings contribute to our understanding of the pathophysiologic effects of histamine on CBF in man and may have practical relevance in patients undergoing treatment with H2 receptor-blocking drugs.