Oligomeganephronia (OMN) is characterized by a reduced number of nephrons, with compensatory hypertrophy of the remaining glomeruli and tubules. The clinico-pathological features of six cases seen at The Hospital for Sick Children, Toronto were reviewed. One patient presented in infancy (10 days of age), the others between 12.8 and 14.5 years (mean 13.7 years), with long-standing polydipsia and polyuria, enuresis, and growth retardation. All patients had proteinuria which tended to increase as the disease progressed. At renal biopsy, four patients showed significant proteinuria (greater than 1.3 g/24 hr). Biopsies from these patients showed focal segmental glomerulosclerosis (FSGS) and all have rapidly progressed to dialysis/transplantation. The two remaining patients had lesser degrees of proteinuria (less than 0.3 g/24 hr) and no evidence of FSGS on biopsy; however, they are currently in chronic renal failure (mean serum creatinine 2.8 mg/dl). We conclude that increasing proteinuria in patients with OMN heralds the development of FSGS, presumably due to functional overload of the reduced nephron number. This is associated with a rapid decline in renal function.