Neurohistochemical and electron microscopic techniques have been used to determine the autonomic innervation of smooth muscle in the normal human male and female bladder neck and proximal urethra. Numerous cholinergic nerves supply the bladder neck and female proximal urethra, although nerves of the noradrenergic type rarely are observed in these regions. In contrast the male proximal urethra is supplied richly with noradrenergic nerves, indicating that the region is under direct sympathetic control and functions to prevent vesical reflux of ejaculate. The sympathetic innervation of the human bladder neck and female proximal urethra is different from that in other species, a finding that emphasizes the need for caution when results obtained from experimental animals are applied to the human. The sex difference is the innervation of the human proximal urethra has been discussed, particularly in relation to autonomic blocking agents currently used in the treatment of bladder neck and urethral dysfunction.