Rats were chronically fed either an ethanol-containing diet (36% of total calories derived from alcohol) or a pair-fed, control diet (no alcohol) for 8 wk, and acute pancreatitis (AP) was subsequently induced by a 3-h i.v. infusion of caerulein (CR) at a dose of 5 micrograms/kg/hr. CR-induced AP in control rats (no alcohol) was characterized by a significant elevation in serum lipase content, pancreatic interstitial edema, infrequent occurrences of karyorrhexis, and the appearance of vacuoles in acinar cells. Chronic feeding of the ethanol diet followed by treatment with CR resulted in increases in serum lipase content, interstitial edema, karyorrhexis, and acinar vacuolization that were significantly greater than that seen in rats fed the control diet and treated with CR. It is concluded that chronic ethanol intake in the rat intensifies AP that is subsequently induced by CR.