The effects of morphine and the opiate antagonist naloxone on human colonic transit were investigated. In a crossover, double-blind fashion, two groups of 6 normal volunteers were studied using colonic transit scintigraphy during the administration of a test drug or control. The test drugs were morphine (0.1 mg/kg every 6 h s.c.) or naloxone (0.8 mg every 6 h s.c.); control was saline (1 ml every 6 h s.c.). Morphine significantly delayed transit in the cecum and ascending colon (p less than 0.05), slowed the progression of the geometric center (p less than 0.01), and decreased the number of bowel movements per 48 h (p less than 0.005). Naloxone accelerated transit in the transverse colon and rectosigmoid colon (p less than 0.05) and accelerated the progression of the geometric center (p less than 0.05), but had no effect on the number of bowel movements per 48 h (p greater than 0.05). These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit.