Relative insulin sensitivity in aging and obesity was studied during 6-h euglycemic-hyperinsulinemic clamp procedures in seven nonobese weight-matched premenopausal (Pre-M) and postmenopausal (Post-M) women and in nine weight-matched obese Pre-M and Post-M subjects. Peripheral glucose disappearance rates (Rd) and endogenous glucose production rates (EGPR) were measured during baseline (0-2 h) and at insulin delivery rates of 10 (2-4 h) and 40 mU/m2.min (4-6 h). Baseline Rd and EGPR were comparable in the four groups. In Pre-M nonobese women, Rd rose 1.6- and 4-fold above baseline, respectively, at 2-4 and 4-6 h. In all other groups Rd did not change at the lower insulin delivery rate and rose only 2-fold above baseline at the higher delivery rate. EGPR was suppressed 61% and 100% at the two insulin infusion rates, respectively, in Pre-M nonobese subjects. Similar normal suppression was observed in Post-M nonobese individuals. However, in both obese groups, EGPR suppression was comparable and significantly less than that in nonobese groups. These results confirm the presence of peripheral tissue insulin resistance in both obese and aging women. However, in aging, unlike obesity, EGPR is normally suppressed by insulin. In addition, aging does not appear to intensify the insulin resistance of obese states when both coexist in the same individual.