Effects of opiates on intestinal motor activity and transport of water and electrolytes have been studied separately in previous investigations. The aim of these experiments was to evaluate simultaneously the effects of a synthetic opiate, loperamide, on motor activity and transport in the human intestine. Jejunal, ileal, and colonic perfusions were performed in 9 healthy volunteers. After application of loperamide (12 mg), cyclically recurring migrating motor complexes in the small intestine occurred at a significantly higher frequency than after application of placebo. This was primarily due to a decrease in the duration of irregular motor activity (phase II). Loperamide increased the transit time in the jejunum but not in the ileum or in the colon. Transport rates of water and electrolytes and transmural electrical potential differences were not significantly affected by the drug. These results suggest that opiates exert their constipating effect by inhibiting phase II-related irregular motor activity.