The role of systemic/metabolic factors in the association of obesity with knee osteoarthritis (OA) was analyzed using radiographic data, metabolic measures, and blood pressure for 3885 American adults aged 45-74 from the U.S. National Health and Nutrition Examination Survey, 1971-1975 (NHANES I). Obesity was associated with both bilateral and unilateral OA, but more strongly with bilateral OA. Controlling for age, sex, serum cholesterol, serum uric acid, diabetes, body fat distribution, and blood pressure did not significantly reduce the association between obesity and knee OA. Findings from these data are not supportive of a metabolic link between obesity and knee OA.