To investigate the possibility that cell death in retinal detachment may occur by reactivation of apoptotic programmed cell death mechanisms. Unilateral retinal detachments were created in adult cats using 0.25% sodium hyaluronate; detached and control retinas were studied at different intervals. Internucleosomal DNA fragmentation (one of the landmarks of apoptosis) was investigated in tissue sections with the TUNEL technique, which uses terminal transferase to label with biotinylated nucleotides the 3'ends of DNA fragments. Sections also were labeled with propidium iodide, which intensely stains pyknotic nuclei. In addition, one time point was selected for analysis with electron microscopy. TUNEL-positive (T+) and propidium iodide-positive (PI+) cells almost never were observed in retinas from control eyes, but they were abundant at defined time points after retinal detachment, appearing almost exclusively in the photoreceptor layer. Their frequency was particularly high 1 to 3 days after detachment but declined rapidly over the next several weeks. T+ cells were still present 28 days after retinal detachment. Electron microscopy also revealed evidence of apoptotic cells after retinal detachment. Results are consistent with the hypothesis that photoreceptor degeneration after retinal detachment occurs through apoptosis, usually associated with intrinsic, programmed cell death mechanisms. The detection of a rapid wave of photoreceptor degeneration seems to suggest that early therapeutic interventions might be recommended; agents capable of interfering with the apoptotic mechanism could have a role in the prevention of cell losses that represent a critical complication of retinal detachment.