This study investigated the role of obesity (body mass index, total body weight, triceps skinfold, subscapular skinfold) compared with other anthropometric variables (body fat distribution, muscularity, elbow breadth, bitrochanteric breadth) in order to explain previously noted sex differences in osteoarthritis of the knee. Anthropometric measures, self-reported symptoms, and knee x-ray data were analyzed for 3,905 adults aged 45-74 years with valid x-ray data from the First National Health and Nutrition Examination Survey, 1971-1975. Prevalence of knee osteoarthritis was 4.9% in women and 2.6% in men. The relative risk for women compared with men increased from 1.57 at 45-54 years to 2.14 at 65-74 years. Adjusting for body mass index and subscapular and triceps skinfolds reduced the sex difference, whereas adjusting for total body weight, body fat distribution, muscularity, and skeletal size increased the sex difference. Body mass index was the variable that best reduced the sex difference when the other variables were included in the analysis; it did not, however, eliminate the sex difference. No sex differences were found in the strength of the association between anthropometric variables and osteoarthritis, nor was there evidence to suggest that obesity is a consequence of knee osteoarthritis rather than a risk factor.