For examining the effects of moderate exercise training on peripheral glucose effectiveness (S(g)(2)*), insulin sensitivity (S(i)(2)*), and endogenous glucose production (EGP), seven men and one woman (24.8 +/- 1.8 years) participated in cycle ergometer training at lactate threshold intensity for 60 min/day, 5 days/week for 12 weeks. Stable-labeled frequently sampled intravenous glucose tolerance tests were performed before and 16 h and 1 week after the last training session. S(g)(2)* (pre 0.71 +/- 0.03 x 10(-2), 16 h 0.85 +/- 0.02 x 10(-2) dl. kg(-1). min(-1)) and S(i)(2)* (pre 12.6 +/- 2.6 x 10(-4), 16 h 19.7 +/- 3.3 x 10(-4) dl. kg(-1). min(-1). [ micro U/ml](-1)), analyzed using the two-compartment minimal model, were significantly elevated 16 h after the last training session. The elevated S(g)(2)* remained higher despite the cessation of exercise training for 1 week (1.00 +/- 0.03 x 10(-2) dl. kg(-1). min(-1)). EGP was suppressed within 20 min after glucose bolus, and the suppression of EGP was followed by their overshoot. The time course of EGP during the intravenous glucose tolerance test remained similar after the training period. In conclusion, moderate exercise training at lactate threshold improves not only peripheral insulin sensitivity but also peripheral glucose effectiveness with no change in the effect of glucose and/or insulin to suppress EGP in healthy humans.