We identified a spontaneous retinal degeneration in two rhesus females with the same father and different, unrelated mothers. We are characterizing the disease to determine if it provides a nonhuman primate model of retinitis pigmentosa, a hereditary retinal disease leading to visual impairment or blindness in 4 of every 1000 humans worldwide. The electroretinogram (ERG) was used to assess retinal function in the affected females and 14 age-matched, unaffected monkeys reared under the same conditions. Retinal photographs and fluorescein angiograms were obtained several times, and in one affected animal retinal pathology was documented by light and electron microscopy at 20 months of age. In both affected females, rod and cone ERG a-wave and b-wave amplitudes were reduced to 15-30% of normal by 7 months of age and declined further by 2 years. By 2 years, rod B-wave implicit times were prolonged. In the first animal, incipient ophthalmoscopic changes were visible by 3 months; at 20 months, histopathological examination revealed virtually complete absence of rod photoreceptors but some preservation of cones, particularly in the central retina. The second animal did not show obvious ophthalmoscopic changes at 7, 14 or 20 months, but at 14 years demonstrates widespread bilaterally symmetrical peripheral degeneration sparing the posterior pole. This animal is negative for herpes B and cytomegalovirus. We are now screening her DNA for candidate gene mutations known to produce human retininis pigmentosa, and efforts are underway to produce offspring by in vitro fertilization-embryo transfer. This spontaneous retinal degeneration closely resembles human retinitis pigmentosa both electrophysiologically and morphologically, and thus could provide a unique primate model of the disease. Because only higher primates share critical structural features of the human retina, including the presence of a macula which is essential for central vision, such a model could greatly facilitate the testing of therapeutic strategies including nutritional and drug treatments, gene therapy and retinal transplantation.