Aims: CYP11B2 gene encodes a key enzyme for the production of aldosterone. Our aim is to investigate the association of -344T/C polymorphism with hypertension in Japanese men. The interaction between genotypes and dietary salt intake was also considered. Methods: Three hundred and ten Japanese male workers participated in this study. Daily salt intake was calculated from a food frequency questionnaire. Melting curve analysis was used to determine CYP11B2 genotypes. Results: There was a significant association between the CT + TT genotype and higher prevalence of hypertension (odds ratio: 3.03; p = 0.014). The association presented in a recessive manner and was strongest in the high-salt intake group (odds ratio: 9.44; p = 0.049). Only in the high-intake group, systolic blood pressure (SBP) was significantly higher in the CT + TT group than in the CC group (p = 0.038). The SBP had a positive correlation with salt intake in the CT + TT group (p for linear trend = 0.021), but not in the CC group (p for interaction = 0.011). Conclusions: CYP11B2 gene -344C/T polymorphism affects the risk of hypertension in Japanese men and high-salt intake levels strengthen this association. This gene-diet interaction warrants further study to elucidate the efficacy of salt restriction as an anti hypertensive therapy in different genotypes. Copyright (C) 2008 S. Karger AG, Basel