The effects of reserpine injections were studied on the morphology of the pancreas in an experimental model for cystic fibrosis, the chronically reserpinized rat. A detailed examination of the tissue was carried out at the light and electron microscopic levels. The nonspecific effects of secondary malnutrition induced by the drug were assessed with a group of animals pair fed with the treated animals. In a companion paper, we show that pancreatic wt, lipase, and GP-2 contents also are affected by reserpine treatment. In this study, we report that no morphologic differences were observed between the exocrine pancreatic tissue of control and pair-fed animals. By contrast, reserpine induced an accumulation of zymogen granules in 60% of the treated animals and a concomitant decrease of the area occupied by the rough endoplasmic reticulum in the same cells. Finally, in all treated animals, at the light and electron microscopic levels, it was observed that some particular regions of the pancreatic tissue were strongly affected. In these regions, numerous autophagic bodies and lysosomes were observed. Cisternae of the Golgi complex were also more distended. Some acinar cells were in the process of lysis. Several vacuolar inclusions were present in some intralobular duct cells. Cellular material was seen in acinar and intralobular duct lumina. In these same regions, distended intralobular ducts and acinar lumina were observed. These last two features have never been reported in the reserpinized rat but are important manifestations of the pathology in cystic fibrosis patients where obstructions of ducts are believed to trigger focal destruction of the pancreatic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)