To study the mechanism(s) of neuronal cell death during scrapie infection, we investigated the expression of Bax and Bcl-2 in brains of hamsters infected with 263K scrapie agent. The expression of Bcl-2 mRNA was significantly decreased in the brains of 263K scrapie-infected hamsters compared with controls, whereas the expression levels of Bax mRNA were significantly increased in scrapie-infected brain. The levels of Bax and Bcl-2 proteins in brains of scrapie and control animals reflected the difference in mRNA levels. Immunoreactivity for Bax and Bcl-2 were found predominantly within neurons. In scrapie-infected brains, the number of neuronal cells positive for Bcl-2 was significantly lower in the hippocampal CA3 region and was decreased in the cerebral cortex, whereas the number of neuronal cells positive for Bax was significantly increased in both regions. The possibility that differential regulation of Bax and Bcl-2 expression may play an important role in neuronal cell death induced by scrapie infection is discussed.