The pathogenesis and molecular basis of nerve cell death which accompanies scrapie infections in sheep are not well understood. Degeneration of neurons in culture caused by prion protein fragments has recently been reported to be consistent with mechanisms of cell death by apoptosis or programmed cell death. Apoptosis activation during prion-related encephalopathies has not yet been established in vivo. We report here the detection of DNA damage consistent with apoptosis in the brain cells of sheep infected with scrapie using laser scanning microscopic analysis of the single cell gel assay. We suggest that this DNA fragmentation is the result of the activation of the mechanisms characteristic of apoptotic cell death.