The familial aggregation of blood pressure (BP) may be partly due to the familial aggregation of obesity, caused by genetic and/or environmental factors that influence both. Gene-obesity interactions are expected to result in different heritability estimates for BP at different obesity levels. However, the latter hypothesis has never been tested. The present study included 1243 monozygotic and 833 dizygotic Han Chinese twins (mean±s.d. age: 37.81 ± 9.82; range: 19.1-81.4) from the Chinese National Twin Registry. Body mass index (BMI) was used as the index of general obesity. The outcome measures were systolic BP (SBP) and diastolic BP (DBP). Quantitative genetic modeling was performed using Mx software. The SBP and DBP heritabilities were 46 and 30%, respectively. The positive correlations of BMI with SBP (r=0.26) and with DBP (r=0.27) were largely due to genetic factors (approximately 85%). Genetic factors, which also influence BMI, account for 6 and 7% of the total variance for SBP and DBP, respectively. The gene-obesity interaction analysis showed that both common and unique environmental influences on SBP increased with increasing levels of BMI, resulting in a lower heritability at higher BMI levels, whereas for DBP the heritability remained unchanged at higher BMI levels. Our results suggest that higher BMIs may reduce SBP heritability through a larger impact of environmental effects. These conclusions may be valuable for gene-finding studies.