Patients with exocrine pancreatic insufficiency may absorb greater than 50% of dietary fat despite the absence of measurable pancreatic lipase activity. Nonpancreatic lipolytic activity was measured in gastric and duodenal aspirates from 5 patients with exocrine pancreatic insufficiency secondary to alcoholism and in aspirates from 5 alcoholics without evidence of exocrine pancreatic dysfunction (controls). Samples were collected under fasting and postprandial conditions. All patients with exocrine pancreatic insufficiency had nonpancreatic lipolytic activity in gastric and duodenal aspirates. Lipolytic activity in gastric aspirates was not significantly different between the patients with exocrine pancreatic insufficiency and the controls during the fasting and postprandial periods. Pancreatic insufficiency was associated with significantly (p less than 0.05) higher nonpancreatic lipolytic activity in the duodenum under fasting conditions. No significant difference between the groups was found in postprandial nonpancreatic lipolytic activity. Nonpancreatic lipolytic activity accounted for approximately 90% of total lipolytic activity at the ligament of Treitz in patients with exocrine pancreatic insufficiency as opposed to 7% in the control subjects. These observations suggest a significant role for nonpancreatic lipolytic activity (lingual lipase and gastric lipase) in fat digestion in patients with pancreatic insufficiency secondary to chronic alcohol abuse.