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 (Rd) 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 Rd, and CHO OX increased synergistically when exercise and insulin clamps were combined. Exercise decreased (P less than 0.05) the half-maximal doses (ED50) and increased the maximal responses (Vmax) for insulin-dependent Rd and CHO OX. Estimates of insulin-independent Rd 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 less than 0.05). The total suppression of free fatty acids (FFA) and fat OX by insulin were elevated by exercise (P less than 0.05). In summary, exercise and insulin interact synergistically in stimulating Rd and CHO OX.(ABSTRACT TRUNCATED AT 250 WORDS)