In order to determine whether apoptosis contributes to the neuronal loss in scrapie, in situ end labeling was applied on brains of mice showing clinical signs of the disease. Positively labeled, apoptotic neurons were observed in the cerebellum, cerebral cortex and hippocampus, areas known to show characteristic scrapie-related vacuolation, and were absent in the brains of control mice. We conclude that apoptosis plays a role in the neuronal loss that occurs in scrapie. The importance of apoptosis as a predominant cell death mechanism in scrapie, however, remains to be determined.