The C825T polymorphism in the GNB3 gene encoding a beta3 subunit from heterotrimeric G-proteins correlates strongly with the variation in activity of the G-proteins. It has so far been associated with a variety of medical conditions, but has not been tested for association with vesico-ureteric reflux (VUR). Primary VUR is a condition of genetic origin that appears to be inherited in an autosomal dominant mode, but with reduced penetrance. The constitutional change in G-protein-mediated cell signaling associated with the C825T polymorphism might be one of the factors that participate in the development of VUR by modifying the effect of still unknown mutated gene(s). A significant difference in genotype frequencies (chi(2) = 7.38, P = 0.025, df = 2) was observed between patients with primary VUR (33 CC homozygotes, 40 CT heterozygotes, 12 TT homozygotes) and healthy controls with no medical record of reflux (114 CC homozygotes, 88 CT heterozygotes, 18 TT homozygotes). This result suggests that the C825T polymorphism of the GNB3 gene might be associated with the development of VUR.