The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.