A middle-aged rhesus monkey with detailed clinical history exhibited progression of a macular abnormality with a variety of clinical drusen and pigment changes typical of the Cayo Santiago phenotype. Numerous frozen sections of one sample of the macular retina/retinal pigment epithelium (RPE)/choroid showed a single classical druse but extensive single and clustered lipid-filled RPE cells. The monkey exhibited functional outer retinal decline and an insignificant number of 'window defects' as found among signs of relatively benign human macular aging. The clinical and histologically defined results agree if lipid-filled RPE cells are included among the clinically apparent signs of drusen. © 2006 American College of Veterinary Ophthalmologists.