The effect of ethanol on pancreatic exocrine secretion was studied in isolated rat pancreatic acini. Ethanol caused a dose-dependent stimulation of amylase release, and a twofold increase of amylase release was observed with 600 mM ethanol. Ethanol inhibited cholecystokinin octapeptide (CCK-8)-and carbamylcholine-stimulated amylase release and similarly inhibited binding of [3 H] CCK-8 and [N-methyl-3 H] scopolamine to isolated rat pancreatic acini in a dose-dependent manner. The inhibitory effect of ethanol was fully reversible with respect to CCK–induced amylase release. On the other hand, ethanol potentiated secretin-and vasoactive intestinal peptide (VIP)-stimulated amylase release. Ethanol induced a small but significant increase in Ca 2+ efflux, whereas CCK-8 induced an immediate and large increase, but ethanol significantly inhibited CCK-% stimulated Ca z+ efflux. The present study clearly demonstrates the dual effects of ethanol on pancreatic exocrine function: stimulation and inhibition. We suggest that mobilization of intracellular Ca 2+ may be involved in the mechanism of ethanol's action on isolated rat pancreatic acini.