The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis of hypertension in comparison with markers of adipose tissue mass (leptin) and inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be clarified. The eligible study population consisted of 2,045 residents aged > or =40 years who had participated in a community-based survey and had complete data for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model assessment of insulin resistance (HOMA-IR) had been calculated from insulin and plasma glucose. Among all eligible participants, as well as in the subgroup of nondiabetic normotensives (blood pressure <140/90 mmHg and without antihypertensive medication), all three markers were significantly correlated with systolic blood pressure (negative correlation for adiponectin and positive correlations for leptin and hs-CRP). Among all participants, systolic blood pressure and the presence of hypertension were determined mainly by age, sex, body mass index, and waist circumference. None of the markers further contributed to the multivariate linear regression or logistic regression models. In contrast, adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated with systolic blood pressure and the presence of pre-hypertension (blood pressure within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and waist circumference in the nondiabetic normotensive subgroup. Similarly, adiponectin was independently associated with diastolic blood pressure in the nondiabetic normotensive subgroup but not in the whole population. In conclusion, adiponectin, but not leptin or hs-CRP, was independently associated with blood pressure in a nondiabetic normotensive subgroup.