Alcohol is recognized as one etiological factor in pancreatitis and according to recent studies, phospholipase A2 (PLA2) may be an important factor in the pathogenesis of this disease. However, the effect of chronic ethanol ingestion on PLA2 activity has not been studied in pancreatitis. To clarify the possible relation of these two factors 48 male Wistar rats received 15% (v/v) ethanol in drinking water for 12 weeks and 48 rats served as controls drinking tap water. Blood samples were collected from the control animals by puncturing the abdominal aorta. Experimental pancreatitis was induced by intraductal retrograde infusion of normal rat bile and blood samples collected 24 hr after the infusion. PLA2 activities in the plasma were measured by using the substrate with a 3H-labeled fatty acid in position 2. PLA2 activities in the control group were 11.2 +/- 1.3 (mean +/- SE) nmole/ml/min and 21.7 +/- 3.5 twenty-four hours later (P less than 0.05). In alcoholic rats the activities were 11.1 +/- 1.4 and 54.0 +/- 10.3, respectively (P less than 0.003). The increase of the activities was greater in alcoholic rats and the difference between the groups statistically significant (P less than 0.025). The mortality rate was 4.2% among the control animals and 29.2% in the alcoholic groups (P less than 0.026). The results of this study suggest that chronic alcohol ingestion makes the pancreas vulnerable to severe pancreatitis with high mortality. This is associated with significantly increased activities of PLA2.