Isolated monkey corpus cavernosum muscle strips contracted with prostaglandin F₂ and treated with prazosin responded to transmural electrical stimulation with frequency-related relaxations that were abolished by tetrodotoxin. The nitric oxide (NO) synthase inhibitor N^G-nitro-L-arginine (L-NNA) significantly attenuated but did not abolish the response; L-arginine reversed the inhibition. The neurogenic relaxation was not influenced in the strips treated with atropine or calcitonin gene-related peptide (CGRP)-(837), a CGRP-receptor antagonist, and those desensitized to vasoactive intestinal polypeptide (VIP) or pituitary adenylate cyclase-activating polypeptide (PACAP). Nerve fibers containing NADPH diaphorase were histochemically demonstrated in cavernous tissues. The relaxant response resistant to the NO synthase inhibitor was abolished by high K⁺ and tetrabutylammonium but was unaffected by glibenclamide, charybdotoxin, apamin, ouabain, SKF-525a, a cytochrome P-450 inhibitor, and oxyhemoglobin. It is concluded that neurogenic relaxations of monkey corpus cavernosum muscle is associated partly with NO released as a neurotransmitter and that other relaxing factor(s) possibly responsible for K⁺ channel opening also participates; however, the type of K⁺ channel involved is not determined. Acetylcholine, VIP, CGRP, PACAP, and the Na⁺ pump do not seem to be involved in the neurogenic relaxation.