Increased protein filtration and work overload have been proposed to account for the development of glomerular sclerosis in old rats. Sprague-Dawley rat kidneys were examined ultrastructurally from birth through 24 months of age to further delineate pathogenetic factors. There was progressive thickening of all basement membranes with lamination, intramembranous pseudolinear deposits, and degeneration. The glomerular basement membrane (GBM) was 1300 A at birth and increased to 4800 A by 24 months of age. GBM thickening correlated very closely with age (r = 0.90, P less than 0.001), correlated roughly with mesangial sclerosis, but did not correlate at all with proteinuria. Obliteration of podocytes and degenerative changes in the cytoplasm occurred in all cell types and was present in both proteinuric and nonproteinuric rats. These findings suggest that the lesion of spontaneous glomerular sclerosis of aging rats results not from proteinuria but from the natural process of abiotrophic involution. Further, this lesion is but a more obvious indicator of the alterations occurring simultaneously in other portions of the kidney.