&NA;To evaluate the possible effect of gastrointestinal neuropeptides on anal function, the effect of somatostatin, enkephalin, VIP, and substance P on anal canal pressure and electromyographic response of the external anal sphincter was studied in healthy subjects. Enkephalin and somatostatin elicited a significant decrease in anal canal pressure after a bolus injection of 1 &mgr;g/kg body weight whereas VIP and substance P had no effect. Future studies must show whether these effects are of pharmacologic importance and if these peptides participate in the physiologic regulation of anorectal function.