Muscle strips, 30 x 3 mm, were cut out in circular direction from the fundus region of the stomach. Mechanical activity was recorded by means of mechanoelectrical force transducers. Vasoactive intestinal peptide (VIP) at concentrations of 10(-9) to 10(-7) M caused a dose-dependent relaxation of muscle strips which was insensitive to tetrodotoxin. Field electrical stimulation (10 Hz, 1 ms, supramaximal voltage) produced contractions, which were blocked by atropine. VIP (10(-9) to 10(-7) M) dose-dependently decreased the amplitude of the electrically-induced contractions. VIP dose-dependently reduced the electrically-stimulated [3H] acetylcholine release. It is suggested that at least two different mechanisms are involved in the VIP-induced relaxation of the gastric muscle: a direct action on the smooth muscle and an indirect action mediated through cholinergic innervation.