To study the effects of ethanol on disulfiram-treated rats, we administered ethanol orally at a does of 2000 mg/kg, twice daily for 5 days. The administration of ethanol or disulfiram alone produced no recognizable changes in pancreatic acinar cells. Ethanol administration, in disulfiram-treated rats resulted in a decrease in the content of zymogen granules in acinar cells, and the appearance of intraplasmic vacuolization. Electron microscopically, these vacuoles appeared on the basal side of nuclei. In addition, similar vacuoles appeared in liver cells, and these vacuolizations seemed to show lipid inclusions. However, ethanol administration to disulfiram-treated rats did not cause inflammatory changes or edema in the pancreas. A comparison of blood ethanol levels in rats receiving ethanol alone and disulfiram plus ethanol showed no significant difference, but acetaldehyde levels in rats receiving ethanol plus disulfiram rats were significantly higher than those in rats receiving ethanol alone. These findings suggested that acetaldehyde caused a decrease of zymogen granules and the presence of lipid inclusions in pancreatic acinar cells.