The present study was designed to investigate general morphology and the response of human deferential artery to constrictor and dilator substances with special emphasis on endothelium-dependent responses. Human deferential artery segments were obtained from patients undergoing radical cystectomy (n = 7), suprapubic prostatectomy (n = 6), or radical prostatectomy (n = 6). Light microscopy revealed that human deferential artery is of muscular type, and fluorescence microscopy showed a dense adrenergic innervation. Paired rings, one normal and the other de-endothelialized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Vasopressin, endothelin, serotonin, and potassium chloride induced endothelium-independent contractions, whereas norepinephrine and electrical field stimulation caused frequency-dependent contractions that were of greater magnitude in arteries denuded of endothelium. In precontracted arterial rings, acetylcholine and substance P induced endothelium-dependent relaxations. In contrast, papaverine and sodium nitroprusside caused concentration-dependent relaxations that were similar in the presence and in the absence of endothelium. NG-nitro-L-arginine methyl ester (10(-4) M), an inhibitor of nitric oxide synthase, potentiated the responses to norepinephrine in artery rings with endothelium, nearly abolished the acetylcholine-induced relaxation, and attenuated the relaxation induced by substance P. incubation with methylene blue (10(-5) M), an inhibitor of guanylate cyclase, completely prevented the relaxation induced by acetylcholine in arteries with endothelium. The results of this study indicate that the human deferential artery has a dense adrenergic innervation and marked ability to contract or relax in response to different agonists. Some of these responses are in part endothelium dependent and mediated through release of nitric oxide. These morphological and pharmacological observations could play an important role in regulating flow or pressure of blood that arrives to the vas deferens.