In a previous study, we reported that the pancreatic wet weight in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, cholecystokinin-A (CCK-A) receptor-defective because of a congenital gene abnormality, was significantly lower than in control rats (Long-Evans Tokushima Otsuka; LETO) from 3 weeks of age. In this study we examined apoptosis of pancreatic acinar cells in OLETF rats at 5 to 6 weeks of age in comparison with that in LET0 rats. We present here direct morphologic evidence of apoptosis in OLETF rats, using a 3′-OH nick end-labeling method for detecting cells with DNAstrand breaks and electron microscopy. Nick end-labeling revealed a sinall number of positively labeled acinar cells in OLETF rats. On electron microscopic examination, small numbers of apoptotic cells were seen in the lobules in OLETF rats but not in LETO rats. These results suggest that apoptosis plays an important role in the destruction of acinar cells of OLETF rats and induces atrophy of the pancreas.