In order to determine whether nicotine acts on corporal smooth muscle, the mechanism of its effect on strips of rabbit corpus cavernosum was studied in vitro. Rabbit corpus cavernosum muscle strips were mounted in an organ bath with modified Krebs-Henseleit solution and aerated with 95% O-2 and 5% CO2. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease of precontraction induced by phenylephrine. Nicotine produced concentration dependent relaxation when preparations were precontracted by phenylephrine (10(-5) M). The maximum nicotine-induced relaxation was 60.4+/-4.2% of the phenylephrine contraction and was not affected by indomethacin (10(-5) M), N-w-nitro L-arginine methyl ester (3x10(-5) M), methylene blue (10(-5) M), glibenclamide (10(-5) M), clotrimazole (10(-6) M), tetraethylammonium (3x10(-4) M), or 4-aminopyridine (10(-3) M). Nicotine did not exhibit a calcium antagonizing effect. From these results, we conclude that nicotine-induced relaxation of the rabbit corpus cavernosum is not mediated by the release of nitric oxide, prostaglandins or a related substance, by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of the action by which nicotine acts on corporal smooth muscle.