Some of the effects of oral contraceptives (OCs) to alter glucoregulation may be ameliorated by exercise. To test this premise, the effects of acute aerobic exercise on postprandial glucose, insulin, and C-peptide responses (area under the curve [AUC]) were measured in 8 users of low-dose estrogen and progestin OCs (OC(+)) and 10 women not using OCs (OC(-)). They completed 2 randomly ordered intervention trials: (1) aerobic exercise on 3 consecutive days with a 2.5-hour, 75-g oral glucose tolerance test (OGTT) on day 4, and (2) no exercise for 3 days prior to the OGTT (control trial). The exercise was 50 minutes of treadmill walking at 70% (.-)VO(2max). The groups were similar in age (27 +/- 3 years), waist-to-hip ratio (0.74 +/- 0.01), and cardiorespiratory fitness (32.5 +/- 1.6 mL x kg body mass(-1) x min(-1)). Fasting plasma glucose, C-peptide, and insulin levels were similar (P >.05) between groups in the control trial. In both trials, glucose(AUC) was significantly greater (13%, P <.05) in OC(+). Exercise resulted in a significant (P <.05) decrease in fasting plasma glucose and insulin, insulin(AUC), glucose(AUC) x insulin(AUC), and C-peptide(AUC) in both groups, suggesting enhanced insulin action and/or reduced pancreatic insulin secretion. Hepatic insulin extraction ([C-peptide(AUC) - insulin(AUC)())]/C-peptide(AUC)) was increased following exercise only in OC(+). Thus, insulin action was enhanced in response to exercise in young sedentary women independent of OC use. The mechanisms for the acute exercise effect on insulin action may be different in OC users compared with normally menstruating women.