Contractile responses of androgen-sensitive smooth muscles such as the vas deferens and seminal vesicles are highly dependent upon the endocrine status of the animal. Although diabetes mellitus produces disturbances in reproductive function, including decreased serum androgen levels, the effects of diabetes on the contractile function of androgen-dependent urogenital smooth muscles have not been conclusively established. The present study compared the effects of streptozotocin-induced diabetes with those of castration on the contractile responses of rat vasa deferentia. Diabetes and castration produced significant decreases in serum testosterone levels, accompanied by significant decreases in vas deferens weights. Contractile responses of vasa deferentia from diabetic rats to carbachol, ATP, and phenylephrine were significantly increased, and responses to nerve stimulation were decreased. Similar results were obtained with vasa deferentia from castrated rats. Castration produced significant increases in contractile responses of vasa deferentia to carbachol and phenylephrine and decreased responses to nerve stimulation. The data suggest that both castration and diabetes produce a denervation-like supersensitivity which is specific for receptor-mediated processes.