The effect of chronic alcohol abuse on the secretion of pancreatic exocrine proteins was studied. Pure pancreatic juice (PPJ) was obtained by endoscopic cannulation of the pancreatic duct from 21 healthy, nonalcoholic volunteers and 25 chronic alcoholics. Peak concentration and output of total proteins after sequential stimulation with secretin and cholecystokinin was elevated significantly in chronic alcoholics when compared to nonalcoholic subjects. The most striking change in the secretory proteins investigated was exhibited by the trypsinogens. Although the concentrations of all three trypsinogen variants were elevated significantly in PPJ of chronic alcoholics, most of the increase resulted from an approximately fivefold increase of the anionic variant, suggesting nonparallel alterations in the synthesis of pancreatic exocrine proteins. Whereas the ratio of cationic-anionic trypsinogen in the control group was consistently greater than one, it was, without exception, below one in the chronic alcoholics group. As there was no significant increase in trypsin inhibitor in PPJ of alcoholics, the ratio of trypsinogen-trypsin inhibitor showed a highly significant increase in this group. This distortion of the normal ratio in favor of trypsinogen may facilitate premature activation of pancreatic zymogens as postulated in acute pancreatitis. The concentrations of other zymogens and lysosomal hydrolases in PPJ of chronic alcoholics showed small, but not significant, increases, with the exception of leucine naphthylamidase which was significantly elevated. Nonparallel secretion of some exocrine proteins previously described in healthy nonalcoholic subjects was affected selectively by chronic ethanol ingestion. Thus, in chronic alcoholics the secretory kinetics of trypsinogen and chymotrypsinogen were altered, but trypsin inhibitor secretion remained apparently unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)