To assess the interaction of exercise and insulin action, healthy males were studied with saline infusion (n = 5) or with a hyperinsulinemic euglycemic clamp (0.5, 1.0, 2.0, or 15.0 mU·kg-1·min-1; n = 5 at each dose) during rest (40 min), moderate-intensity cycle exercise (100 min), and recovery (100 min). Metabolism was assessed using isotopic methods and indirect calorimetry. During rest, exercise, and recovery with saline infusion, plasma glucose was unchanged, total glucose utilization (R(d)) was 2.4 ± 0.4, 4.9 ± 0.2, and 2.6 ± 0.2 mg·kg-1·min-1, and carbohydrate (CHO) oxidation (OX) was 1.4 ± 0.3, 10.6 ± 1.1, and 0.5 ± 0.2 mg·kg-1·min-1. The glucose infusion, insulin-dependent R(d), and CHO OX increased synergistically when exercise and insulin clamps were combined. Exercise decreased (P < 0.05) the half-maximal doses (ED50) and increased the maximal responses (V(max)) for insulin-dependent R(d) and CHO OX. Estimates of insulin-independent R(d) were 1.3 ± 0.7, 4.1 ± 1.3, and 1.9 ± 0.7 mg·kg-1·min-1 and insulin-independent CHO OX were 1.2 ± 0.9, 10.4 ± 1.3, and 0.6 ± 0.3 mg·kg-1·min-1 during rest, exercise, and recovery. Estimates during exercise were greater than those at rest (P < 0.05). The total suppression of free fatty acids (FFA) and fat OX by insulin were elevated by exercise (P < 0.05). In summary, exercise and insulin interact synergistically in stimulating R(d) and CHO OX. Although exercise lowers the ED50 and increases the V(max) of insulin on R(d) and CHO OX, most of the exercise-induced rise in these processes occurs independently of insulin action. Finally, the magnitude of insulin's suppressive effect on FFA levels and fat OX are increased by exercise.