An electron microscopic study of the nonsclerotic glomeruli or nonsclerosed segments of affected glomeruli was made in 34 children with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) and in 34 children with minimal-change nephrotic syndrome. Particular attention was paid to alterations of glomerular epithelium. The most striking glomerular change in FSGS was vacuolation of the epithelial cell. Glomerular epithelial vacuolation was found in 21 of the 34 patients with FSGS. Eleven of these 21 patients with vacuoles developed chronic renal failure, while only one of the 13 patients without vacuoles developed renal failure. In minimal-change nephrotic syndrome only five of the 34 patients showed mild epithelial vacuolation. These observations are consistent with glomerular epithelial vacuolation contributing to the development and progression of the glomerular lesion in FSGS.