The polymorphism C825T of the gene encoding the G-protein beta 3-subunit (GNB3) was found to be associated with an increased prevalence of hypertension in a number of studies. The aim of the present study was to investigate the association between this polymorphism and blood pressure phenotypes in an urban, large and ethnically mixed population of Brazil. 2. Individuals (n=1,568) were randomly selected from the general population of the Vitória City metropolitan area. The GNB3 C825T polymorphism was genotyped in each individual. Baseline cardiovascular risk factors were collected for all participants. Cardiovascular risk variables and genotypes were compared using anova and the Chi-squared test for univariate comparisons and logistic regression for multiple comparisons. 3. A statistically significant interaction between the 825T allele and obesity was observed for systolic blood pressure (SBP; P=0.02). In fact, the C825T genotype was predictive of SBP only in individuals with increased body mass index (P=0.02). In addition, in a multiple logistic regression model conducted in the obese population and adjusted for age, sex, ethnicity, diabetes, triglycerides and total cholesterol, the presence of the T allele was significantly associated with a 1.5-fold (95% confidence interval 1.04--2.26) increased risk of hypertension. Lack of statistical power does not explain the absence of other positive gene-environment interactions. 4. The present results suggest that an important gene yen environment interaction may take place between bodyweight regulation and the GNB3 gene. This finding provides further evidence for a role of the 825T allele in hypertension susceptibility and may be used for better disease stratification.