The effects of alcohol intoxication on serum amylase levels were tested in both normal subjects and chronic alcoholics. Paired samples of ethanol levels and isoamylase levels in the normal subjects (n = 11) showed a rise in both total serum amylase (P less than 0.01) and nonpancreatic isoamylase (P less than 0.05) after drinking. Unpaired cohort groups of sober chronic alcoholics at a rehabilitation facility (n = 46) and intoxicated chronic alcoholics in an emergency room (n = 58) were also compared. Average blood alcohol levels in the intoxicated controls were 93 mg% compared to a level of 301 mg% in the intoxicated chronic alcoholic. Intoxication superimposed on chronic alcoholism caused a moderate rise in the total serum amylase (NS) and a significant elevation of the nonpancreatic isoamylase (P less than 0.01). Sober chronic alcoholics had a significantly greater average total serum amylase (P less than 0.001) and nonpancreatic isoamylase (P less than 0.01) than the normal controls. No difference in the average pancreatic isoamylase levels was seen in any group. These data suggest a biphasic response to alcohol on the serum amylase level. Acute and chronic changes appear to operate independently. The cause for these effects is speculative. Isoamylase analysis is needed in the alcoholic population to sort out the meaning of hyperamylasemia.