A histological review of 86 pediatric nephrectomy specimens from patients with vesicoureteric reflux (with or without apparent obstruction at the vesicoureteric junction) investigated the relationship between the presence and extent of focal and segmental glomerulosclerosis (FSGS) and coexisting renal hypoplasia and postnatally acquired cortical damage. FSGS was found in 18 patients, 9 of whom were less than 5 years old. There was no significant association between the presence (or grade) or absence of FSGS and age at nephrectomy, gender, presence or absence of obstruction, and severity of hypoplasia and/or postnatally acquired cortical loss. FSGS was absent from 18 hypoplastic kidneys without vesicoureteric reflux (although of relatively young age), 40 normally developed kidneys age-matched with the index population, and 72 nephrectomy specimens without vesicoureteric reflux (except in 2 known cases of focal segmental glomerulonephritis). Within the index population FSGS was significantly (P < .01) associated with hypertension, and hypertension was significantly associated with proteinuria (P < .001) but not with an abnormal contralateral kidney. There was no significant association between FSGS, proteinuria, and an abnormal contralateral kidney. Our results were unexpected when interpreted within a pathogenesis for FSGS of glomerular "hyperfiltration." They may, at least in the pediatric age group, indicate a possible role for other mechanisms in the development of FSGS.