The regulation of adrenergic activity in the penis was investigated by studying human and rabbit corpus cavernosum strips in organ chambers and measuring the release of norepinephrine from adrenergic nerve terminals. Electrical field stimulation of corporal strips caused frequency-dependent contractions which were potentiated by cocaine and attenuated by the alpha 1 adrenoceptor antagonist prazosin (10(-7) M), but not by the alpha 2 adrenoceptor antagonist rauwolscine (10(-7) M). Norepinephrine caused concentration-dependent contractions of corporal strips, which were attenuated by prazosin and rauwolscine. Acetylcholine and physostigmine attenuated adrenergic nerve mediated contractions and also significantly reduced electrically-induced norepinephrine release. These effects were reversed by atropine. Atropine alone enhanced electrically-induced norepinephrine release. Rauwolscine inconsistently enhanced adrenergic nerve mediated contractions but augmented norepinephrine release caused by electrical stimulation. The alpha 2 adrenoceptor agonist clonidine inhibited electrically-induced norepinephrine release. Vasoactive intestinal polypeptide (VIP) attenuated adrenergically-mediated contractions, but had no effect on electrically-induced release of norepinephrine. It is concluded that: 1) contraction of corporal smooth muscle is mediated by postjunctional alpha 1 adrenoceptors; 2) adrenergic activity is modulated by prejunctional alpha 2 adrenoceptors and cholinergic nerves via prejunctional muscarinic receptors; and 3) the putative nonadrenergic noncholinergic neurotransmitter, VIP, has no apparent role in the regulation of adrenergic nerves.