To elucidate the injurious effects of alcohol on the human pancreas, serum pancreatic enzymes were followed for the first 2 months of abstinence in 31 asymptomatic alcoholics. Sequential declines of serum enzymes were observed in immunoreactive human pancreatic elastase 1 and trypsin (IRE and IRT) as well as gamma-glutamyl transpeptidase (gamma-GTP), creatine phosphokinase (CPK) and glutamate-oxaloacetate transaminase (GOT) during the abstinence. The incidence of abnormally high enzyme activities found initially changed by the end of 2 months of abstinence as follows: from 55 to 6% for IRE, from 25 to 0% for IRT, from 3 to 6% for amylase, from 76 to 22% for gamma-GTP, from 69 to 39% for CPK, from 55 to 12% for GOT, and from 38 to 12% for GPT, respectively. The decline suggests that excessive intake of alcohol enhances the escape of the enzymes from the pancreas into the serum, probably altering membrane permeability or cellular metabolism of the pancreas, a direct toxic effect of alcohol.