To evaluate insulin sensitivity and responsiveness, a two-stage hyperinsulinemic euglycemic clamp procedure (insulin infusions of 40 and 400 mU·m-2·min-1) was performed on 11 endurance-trained and 11 untrained volunteers. A 3-h hyperglycemic clamp procedure (plasma glucose ~180 mg/dl) was used to study the insulin response to a fixed glycemic stimulus in 15 trained and 12 untrained subjects. During the 40-mU·m-2·min-1 insulin infusion, the glucose disposal rate was 10.2 ± 0.5 mg·kg fat-free mass (FFM)-1·min-1 in the trained group compared with 8.0 ± 0.6 mg·kg FFM-1·min-1 in the untrained group (P < 0.01). In contrast, there was no significant difference in maximally stimulated glucose disposal: 17.7 ± 0.6 in the trained vs. 16.7 ± 0.7 mg·kg FFM-1·min-1 in the untrained group. During the hyperglycemic clamp procedure, the incremental area for plasma insulin was lower in the trained subjects for both early (0-10 min: 140 ± 18 vs. 223 ± 23 μU·ml-1·min; P < 0.005) and late (10-180 min: 4,582 ± 689 vs. 8,895 ± 1,316 μU·ml-1·min; P < 0.005) insulin secretory phases. These data demonstrate that 1) the improved insulin action in healthy trained subjects is due to increased sensitivity to insulin, with no change in responsiveness to insulin, and 2) trained subjects have a smaller plasma insulin response to an identical glucose stimulus than untrained individuals.