Vasoactive intestinal peptide (VIP) had two types of effects on the longitudinal muscle of the mouse distal colon. At low concentrations (10(-8) M) VIP induced a contraction which seemed to be related to the production of prostaglandins as it was abolished after preincubation with indomethacin (10(-6) M). At higher concentrations (3 X 10(-8) and 10(-7) M) VIP induced relaxations which developed slowly and were related to stimulation of the adenylate cyclase activity of the smooth muscle cells. There is no evidence that VIP is the non-adrenergic, non-cholinergic transmitter released by electrical stimulation in this preparation and responsible for rapid relaxation of the smooth muscle.