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An unusual condition of the inferior retinal pigment epithelium (RPE) and neural retina has been observed in essentially all the large bullfrogs examined (Rana catesbeiana, 13 to 20 cm body length, supplied from the U.S. West Coast and Midwest). By ophthalmoscopy the inferior fundus exhibited numerous white spots and lines, which were found by light microscopy to be overlain by smaller black dots and lines. Closer examination revealed that the light areas were regions of depigmented RPE and that the black dots and lines were melanosome-laden macrophages within the adjacent retina. Further examination by light microscopy and electron microscopy allowed the formulation of the following sequence. (1) Monocytes in the choroidal capillaries crossed Bruch's membrane and passed vitreally between adjacent RPE cells. (2) In the subretinal space monocytes transformed into phagocytic macrophages, which became engorged with melanin granules and other RPE inclusions, whereas nearby RPE cells became much thinner and very depigmented. (3) The pigment-laden macrophages then moved vitreally into the avascular neural retina. Although in most areas only the RPE appeared affected by macrophage invasion, occasional localized photoreceptor disruption occurred. The severity of the lesion varied with frog size, being pronounced in large frogs, moderate in medium-sized animals, and absent in small frogs. Because the pigmentary changes were localized to the inferior part of the eye (which receives the most light from the sun overhead) of large bullfrogs (which are likely old), this phenomenon may be due to a change in RPE melanin granules resulting from the cumulative effect of light exposure.