The G-protein beta3 subunit 825 TT genotype has been associated with obesity and hypertension. We examined the interaction between the G-protein TT genotype, physical activity and body mass index (BMI) in a cross-sectional study of African immigrants and African Americans. The genotype frequencies were 6.3% CC, 37.7% CT, and 56% TT. After adjusting for potential confounders, BMI was found to be significantly higher in the sedentary than in the physically active participants (p=0.045). There was no statistically significant effect for genotype (p=0.215) or the interaction between genotype and the level of physical activity (p=0.219). However, the individuals with the CC or CT genotype who were physically active had substantially lower BMIs (M+/-SE) (i.e., 25.74+/-2.02) than any of the other groups: sedentary CC + CT (30.58+/-1.03), sedentary TT (30.65+/-1.00) or active TT (29.43+/-1.65). Because of the low statistical power of this study, further research is needed to confirm these findings and to explore potential gene-environment/lifestyle interactions.