In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10(-6) M, NG-nitro-L-arginine (L-NNA) 10(-7)-10(-4) M, and oxyhaemoglobin 10(-5) M, but not by methylene blue (MB) 10(-5) M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M, but were unaffected by pyrogallol 10(-4) M, MB 10(-5) M, and tetrodotoxin 10(-6) M. MB 5 x 10(-4)-10(-4) M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10(-7)-10(-4) M and sodium nitroprusside 10(-9)-10(-4) M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10(-5) M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10(-5) M. The response to sodium nitroprusside was unaffected by L-NNA 10(-4) M, oxyhaemoglobin 10(-5) M, and pyrogallol 10(-4) M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10(-5) M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)