To study the development of acute pancreatitis after intraductal trypsin instillation, at 4 hours, 1, 2, 4 and 6 days after this treatment and after instillation of physiologic saline viable acinar cells were isolated from rat pancreas. Gross anatomic and histologic findings were used to evaluate the time course of pathomorphologic changes. The isolated cells were incubated at 37-degrees-C in Eagle's medium in a shaking water bath and the time course of their damage was studied. Additionally, by means of the active accumulation of the fluorophore rhodamine 6 G alterations of the mitochondrial membrane potential, an important parameter of the cellular energy metabolism was evaluated. The most severe histological damage was seen 1 and 2 days after trypsin instillation. At the same time yield and survivability of cells isolated, and their mitochondrial membrane potential reached a minimum. In the controls the time course of these parameters was very similar, but their decrease was less pronounced. Since a direct action of trypsin on acinar cells cannot be responsible for the findings presented a possible involvement of inflammatory cells and their products in the alteration of the cells and of their energy metabolism must be considered.