To investigate the effect of testosterone on contractile tone of endothelium-denuded human corpus cavernosum strips. Human studies designed to examine a possible relaxant effect of testosterone on corpus cavernosal circulation are lacking.Testosterone (0.1-300 μM) was added cumulatively to organ baths after precontraction of isolated human corpus cavernosum strips (n = 5) with KCl (45 mM). Testosterone-induced responses were tested in the presence of nonselective, large, conductance Ca 2+ -activated and voltage-sensitive K + channel inhibitor tetraethylammonium (1 mM), adenosine triphosphate-sensitive K + channel inhibitor glibenclamide (10 μM), voltage-dependent inward rectifier K + channel inhibitor barium chloride (30 μM) and voltage-sensitive K + channel inhibitor 4-aminopyridine (1 mM).Testosterone (0.1-300 μM) produced relaxation in human corpus cavernosum (maximum relaxation 65.4% ± 3.3% of KCl-induced contraction) that reached a maximum at a concentration of 300 μM. Testosterone-induced relaxation was significantly attenuated by glibenclamide, but it was not affected by the other K + channel inhibitors (tetraethylammonium, barium chloride, or 4-aminopyridine).Testosterone might induce relaxation in human isolated corpora cavernosa strips by activation of smooth muscle adenosine triphosphate-sensitive K + channels. This finding suggests that testosterone, in addition to its known endothelial action, might regulate erectile function locally by its action on the smooth muscle of the human corpus cavernosum.