PURPOSE: To determine the pathogenetic mechanism of photoreceptor cell degeneration in the inherited retinal dystrophy in Royal College of Surgeons (RCS) rats. METHODS: The dystrophic retinas of the pink-eyed RCS (RCS-rdy-p) rats were examined for DNA fragmentation by agarose gel electrophoresis of retinal DNA and by TdT-mediated biotin-dUDP nick-end labeling (TUNEL) in paraffin sections. Rats ranging in age from 3 to 60 days were examined. RESULTS: Agarose gel electrophoresis of retinal DNA isolated from animals 25, 30, 35, and 40 days old showed a ladder pattern of degradation with bands corresponding to multiples of 180 to 200 base pair subunits. TUNEL study showed increasing labeling of photoreceptor cells with progression of the retinal dystrophy of the RCS rats. CONCLUSIONS: Apoptosis is the dominant mechanism of photoreceptor degeneration in the RCS rat, which has a genetic defect in the phagocytic activity of retinal pigment epithelium. The onset of the degeneration appeared to vary between rod cells in the different regions of the eye.