Studies have shown that insulin resistance increases with age, independent of changes in total adiposity. However, there is growing evidence that the development of insulin resistance may be more closely related to abdominal adiposity. To evaluate the independent effects of aging and regional and total adiposity on insulin resistance, we performed hyperinsulinemic euglycemic clamps on 17 young (21-33 yr) and 67 older (60-72 yr) men and women. We assessed FFM and total and regional adiposity by hydrodensitometry and anthropometry. Insulin-stimulated GDRs at a plasma insulin concentration of ∼450 pM averaged 45.6 ± 3.3 μmol·kg FFM-1·min-1 (mean ± SE) in the young subjects, 45.6 ± 10.0 μmol·kg FFM-1·min-1 in 24 older subjects who were insulin sensitive, and 23.9 ± 11.7 μmol·kg FFM-1min-1 in 43 older subjects who were insulin resistant. Few significant differences were apparent in skin-fold and circumference measurements between young and insulin-sensitive older subjects, but measurements at most central body sites were significantly larger in the insulin-resistant older subjects. Waist girth accounted for >40% of the variance in insulin action, whereas age explained only 10-20% of the total variance and <2% of the variance when the effects of waist circumference were statistically controlled. These results suggest that insulin resistance is more closely associated with abdominal adiposity than with age.