Insulin action is enhanced in people who exercise regularly and vigorously. In the present study, the hyperinsulinemic, euglycemic clamp procedure was used to determine whether this enhanced insulin action is due to an increased sensitivity and/or an increased responsiveness to insulin. To avoid the variability that exists between individuals and complicates cross-sectional studies, the same subjects were studied in the trained exercising state and again after 10 days of physical inactivity. When the plasma insulin concentration was maintained at approximately 78 microU.ml-1 (a submaximal level), glucose disposal rate averaged 8.7 +/- 0.5 mg.kg-1.min-1 before and 6.7 +/- 0.6 mg.kg-1.min-1 after 10 days of activity (P less than 0.001). When the plasma insulin concentration was maintained at approximately 2,000 microU.ml-1 (a maximally effective concentration), the rate of glucose disposal was not significantly different before (15.3 +/- 0.5 mg.kg-1.min-1) compared with after (14.5 +/- 0.4 mg.kg-1.min-1) 10 days without exercise. These results provide evidence that the reversal of enhanced insulin action that occurs within a few days when exercise-trained individuals stop exercising is due to a decrease in sensitivity to insulin, not to a decrease in insulin responsiveness.