Transforming growth factor-beta1 (TGF-beta1) is an important regulator of blood pressure (BP) and vascular remodeling, and thus may contribute to the pathogenesis of hypertension. A T-->C transition at nucleotide 869 of the TGF-beta1 gene results in a Leu-->Pro substitution at amino acid 10 of the signal peptide. We have now examined the possible association of the 869T-->C polymorphism of the TGF-beta1 gene with BP and the prevalence of hypertension in 2241 community-dwelling Japanese individuals (1126 men and 1115 women). TGF-beta1 genotype was determined by an allele-specific polymerase chain reaction method. For women, both systolic and diastolic BP was significantly higher in individuals with the CC genotype than in those with the TT or TC genotype. No significant association between TGF-beta1 genotype and BP was detected in men. The frequency of the CC genotype was significantly higher in women with hypertension than in those with normal BP. These results suggest that the TGF-beta1 gene at chromosome 19q13.1 may be a candidate susceptibility locus for hypertension in Japanese women.