We used the euglycemic clamp to assess the effects of exercise on maximally insulin-stimulated glucose disposal. In 11 young men, a 60-min bout of exercise had no significant effect on the rate of glucose disposal during a euglycemic clamp performed approximately 30 min postexercise in which plasma insulin was raised to approximately 2,500 microU/ml (a maximal insulin stimulus). The maximal rate of glucose disposal attained during the clamp averaged 15.7 +/- 1.0 mg.kg lean body mass-1.min-1 after exercise vs. a control value of 15.4 mg.kg lean body mass-1.min-1. In a second experiment, eight men performed supine cycle exercise during the 3rd h of a 4-h euglycemic clamp with a plasma insulin concentration of approximately 2,500 microU/ml. Exercise during the hyperinsulinemic clamp resulted in a 70% increase in glucose disposal rate. There was no measurable increase in glucose 6-phosphate in the quadriceps muscle during the insulin infusion at rest. We conclude that prior exercise does not enhance maximally insulin-stimulated glucose disposal in young healthy men. Our results are compatible with the interpretations that glucose availability rather than glucose metabolism limits the rate of glucose disposal in response to a maximal insulin stimulus in resting subjects and that the increase in glucose uptake in response to superimposed exercise is primarily due to an increase in glucose availability.