Dispersed rat pancreatic acini were used to determine the effect of galanin on the exocrine pancreas and on basal and secretagogue-stimulated amylase secretion. Basal amylase secretion and amylase release stimulated by cholecystokinin octapeptide, bombesin, 12-o-tetradecanoyl-phorbol-13-acetate (TPA), secretin, and vasoactive intestinal peptide were not affected by galanin in doses ranging from 10(-12) to 10(-6) M. Galanin, however, significantly inhibited the amylase release stimulated by sub- and supramaximal doses of carbachol. A time course study showed that the inhibition by galanin occurred during the sustained phase of carbachol-stimulated amylase secretion. The inhibitory action of galanin disappeared in acini obtained from animals pretreated with pertussis toxin (PTX). These results suggest that galanin inhibits carbachol-stimulated amylase secretion through a mechanism related to a PTX-sensitive G protein.