We investigated the effect of hyperthyroidism on the responsiveness of the rabbit corpus cavernosum smooth muscle. In male albino rabbits, hyperthyroidism was established by oral feeding of L-thyroxine at increasing dosages (150-450 mug/kg) over an 8-week period. This treatment produced a stable hyperthyroid state as indicated by the increased serum T-4 levels. The reactivity of corpus cavernosum tissue from hyperthyroid animals and euthyroid control animals was studied in organ chambers. Hyperthyroidism caused impaired neurogenic and endothelium-dependent relaxant responses with decreased E-max and pD(2) values. However, hyperthyroidism had no effect on both phenylephrine- and KCl-induced contractile responses and sodium nitroprusside- and papaverine-induced endothelium-independent relaxant responses, and there was no change in agonist potency. These data indicate that hyperthyroidism may impair both neurogenic and endothelium-dependent relaxation of corporal smooth muscle, and may contribute to the etiology of impotence. (C) 2001 Elsevier Science B.V. All rights reserved.