The purpose of this study was to determine the relaxant effects of acetylcholine after inhibition of vascular histaminergic receptors. In isolated rings of the rat pulmonary artery precontracted by phenylephrine (10~5 mol/1) both histamine (10-7 to 10-4 mol/1) and acetylcholine (10-8 to 3xl0-5 mol/1) produced concentration-dependent relaxations. The arterial relaxations induced by either histamine or acetylcholine were markedly reduced or abolished by administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (10“5 mol/1). Relaxant responses to histamine were not influenced by cimetidine, histamine H2-receptor antagonist, but were significantly decreased or abolished by treatment with chlorphenyramine or diphenhydramine, histamine Hi-receptor antagonists. On the other hand, chlorphenyramine and diphenhydramine did not prevent the appearance of endothelium-dependent relaxation to acetylcholine. The results suggest that relaxation to histamine in the rat pulmonary artery is mediated by Hi-histaminergic receptors and their inactivation docs not interfere with the endothelial capability to produce and/or release nitric oxide by the activation of other types of receptors.