The pancreatic acinar cell is potentially the initial site of injuries typically associated with the activation of zymogens that lead to acute pancreatitis. These injuries can occur as a result of alcohol toxicity. a-Chymotrypsin (a-CT) can be activated by alcohols, but the degree of activation is inversely proportional to the alcohol chain length. Methanol (20 %, v/v) causes the more significant effect, with a 12-fold increase in a-CT activity. Although still significant, the activation by ethanol (20 %, v/v) is considerable smaller (4.5-fold), decreasing with  20 % (v/v) propanol and iso-propanol (2.5-fold, each). These alcohols decreased the a-CT affinity for the substrate p-nitrophenyl acetate, but increased k_cat resulting in a higher catalytic efficiency. Differential scanning calorimetry studies are indicative that the effect of alcohols on a-CT is similar to that reported by Velicelebit & Sturtevant (Biochemistry 18 (1979) 1180) for lysozyme, the melting temperature (Tm) decreasing with increasing alcohol concentrations and/or longer alkyl chain. The calorimetric enthalpy increases with the alcohol concentration and the transitions become broader, deviating from the two-state mechanism. Only small changes in a-CT secondary and tertiary structures were observed by circular dichroism and fluorescence measurements. The observed results suggest a synergistic effect of alcohols in acinar cells since zymogen activation is certainly not the only factor involved in the autodigestion of the pancreas.