The associations of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha, and fibrinogen) with anthropometric and metabolic variables were examined in a sample of 112 postmenopausal women not receiving hormone therapy. Body fat distribution was measured by computed tomography, and insulin sensitivity was determined by an euglycemic-hyperinsulinemic clamp. hs-CRP (0.10 < or = r(2) < or =0.37) and IL-6 (0.06 < or = r(2) < or =0.31) were significantly associated with anthropometric and metabolic variables, including visceral and subcutaneous adipose tissue, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein (HDL) cholesterol, and insulin sensitivity (p <0.05). Women with greater hs-CRP concentrations showed deterioration in their metabolic risk profiles, including abdominal obesity, greater triglyceride and lower HDL cholesterol concentrations, and lower insulin sensitivity compared with women with lower hs-CRP levels. Fifty-nine percent of women with high hs-CRP concentrations had the metabolic syndrome as recently defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. After adjustment for visceral adipose tissue, most of the differences in the plasma lipid-lipoprotein profile were eliminated between women with high hs-CRP levels and women with low hs-CRP levels, whereas some differences in blood pressure variables, insulin sensitivity, and inflammatory markers (IL-6 and fibrinogen) remained significant. In conclusion, these results suggest that increased visceral adipose tissue levels appear to be a determinant covariable of the association between high hs-CRP concentrations and alteration in the metabolic profile.