An ultrastructural study of the retina of a patient with advanced retinitis pigmentosa revealed an orderly process of cone degeneration with more advanced stages in the perifovea and less advanced stages in the fovea. No rod photoreceptors were seen. Remaining cones had enlarged nuclei with autophagic vacuoles and bundles of parallel undulating 12 nm filaments in the cytoplasm. In the foveola and fovea cone outer segments were very truncated or absent, although synaptic pedicles were intact. In the perifovea many cone cell bodies were rounded with loss of synaptic pedicles. Pigment epithelial cells underlying remaining cones were enlarged with apically displaced nuclei, occasional phagosomes and large amounts of melanolysosomes. The pigment epithelial cell layer anterior to the perifovea contained flattened pigment epithelial cells without melanolysosomes and macrophage-like cells without pigment. Pigment-laden epithelial cells around atrophic blood vessels in the midperipheral retina showed only round pigment granules unlike the smaller elongated pigment granules observed in retinal pigment epithelial cells in situ. The advanced stage and structural abnormalities in photoreceptors and pigment epithelial cells preclude assigning a primary site for the defect.