Polymorphisms in the Regulator of G-protein Signaling 2 (RGS2) gene have been reported to be associated with hypertension (HT) in Japanese women and black Americans of either gender but not in white Americans or Japanese men. We have tested whether these proposed ethnicity- and gender-specific associations between RGS2 gene polymorphisms and HT can be confirmed in an independent population of male and female blacks, whites, and south Asians.A population-based sample of 1379 black, white Dutch, and south Asian subjects from the Amsterdam area was genotyped for eight polymorphisms in the RGS2 gene. All analyses were done separately per ethnic group. The phenotype high blood pressure was defined as a dichotomous variable comparing HT vs. normotension (NT) and as a linear variable using systolic blood pressure (SBP) in a multiple regression analysis with concomitant antihypertensive medication, age and body mass index as coexplanatory variables.Ethnic differences in the frequency of polymorphisms and haplotypes (HAPs) derived thereof were in line with previous studies. Our data do not confirm previously reported ethnicity- or gender-specific associations regardless which phenotype definition was used. While the D allele of 1891-1892TC insertion/deletion polymorphism showed association in several groups, they differed from previously reported ones. Haplotype-phenotype analysis was not more sensitive to detect genotype-phenotype associations than individual alleles.Previously reported ethnicity- and gender-specific associations of RGS2 genotype and hypertensive phenotype are not robust. Nevertheless, the 1891-1892TC insertion/deletion polymorphism warrants further investigation.