Persistent proteinuria, chronic renal failure, and focal segmental glomerulosclerosis developed in three children with solitary kidneys. Two of these children were born with unilateral kidneys. The third had bilateral reflux and underwent a unilateral nephrectomy and reimplantation of the remaining ureter; persistent proteinuria developed 7 years later. It is postulated that hyperperfusion of a critical number of glomeruli during childhood may be the mechanism responsible for the production of focal segmental glomerulosclerosis in these patients.