Epidemiological evidence on gene-environment effects of the G-protein beta-3 subunit C825T polymorphisms and sodium on blood pressure in the free-living general population is limited. We examined the associations between the C825T polymorphism and blood pressure levels, stratified by the sodium variables estimated by 24-h urinary sodium excretion and a dietary questionnaire, among 1,471 men and women aged 30-74 from a community in Japan. Our a priori hypothesis was that individuals with the 825T allele have elevated blood pressure among subjects with a high sodium intake. Among the whole group, the systolic blood pressure level was +2.2 mmHg (p = 0.10) higher in TT than CC genotype individuals after adjustment for sex, age, antihypertensive medication use, body mass index, and alcohol consumption. This difference was more evident among individuals with low sodium excretion (+4.5 mmHg, p = 0.01), low present sodium intake (+3.2 mmHg, p = 0.11), and low past sodium intake (+4.8 mmHg, p = 0.02). No associations were observed among those with high sodium variables. Our results indicate that the G-protein beta-3 subunit C825T polymorphism is associated with higher systolic blood pressure levels in a large free-living Japanese population, and more specifically in women with a low sodium intake. This finding helps to explain part of the discrepancy between the previously reported genetic association among different ethnic groups.