It has long been assumed that the brainstem exerts a tonic descending inhibitory influence on spinal sexual reflexes, but the source of this inhibition is unknown. Sexual responses (penile erection and ejaculatory movements) were elicited in anesthetized male rats using urethral stimuli. Using brainstem transections and electrolytic and neurotoxic lesions, we have identified a group of neurons in the paragigantocellular reticular nucleus in the ventral medulla which mediates this descending inhibition. Correlative neuroanatomical studies indicate that the inhibition is mediated via a direct projection to pelvic efferent neurons and interneurons. These results promise new approaches to the treatment of human sexual disorders.