OBJECTIVE To determine the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphism in promoting renal scarring among patients with vesicoureteric reflux (VUR). This genetic variant involves a guanosine to adenine transition at position -308, and this single-base polymorphism is associated with increased transcription of the TNF-alpha gene. Recent studies suggest that the TNF-alpha gene may be associated with predisposition to renal scarring. METHODS A total of 195 (51.8% females) patients with VUR demonstrated by voiding cystourethrogram were recruited, 126 of them with reflux nephropathy diagnosed by dimercaptosuccinic scan. The control group included 266 healthy individuals. Genotyping was performed by polymerase chain reaction and digestion with a restriction enzyme. RESULTS Allele frequencies of -308G and -308A were 83.8% and 16.2%, respectively in patients with VUR and 88.9% and 11.1%, respectively in controls (P<0.05). No differences were found in genotype distribution related to presence/absence of renal scars. There was no relationship between TNF-alpha genotype and grade of VUR or the presence of proteinuria. CONCLUSIONS Our data suggest that the TNF-alpha AA genotype is not associated with reflux nephropathy. The TNF-alpha-308A allele could be related to a higher susceptibility to VUR.