Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg · kg fat-free mass (FFM)⁻¹ · min⁻¹; oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean ± SD; 47 ± 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU · m⁻² · min⁻¹) and [6,6-²H₂]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption (V˙o _2 max), and physical activity energy expenditure (²H₂ ¹⁸O kinetics) as possible correlates of glucose disposal.V˙o _2 max was the strongest correlate of glucose disposal (r = 0.63, P < 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from −0.32 to −0.46, P< 0.05 to P < 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of V˙o _2 max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat (r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for V˙o _2 max.V˙o _2 max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance ofV˙o _2 max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.