When moderate exercise begins, O2 uptake (VO2) reaches a steady state within 3 min. However, with heavy exercise, VO2 continues to rise beyond 3 min (VO2 drift). We sought to identify factors contributing to VO2 drift. Ten young subjects performed cycle ergometer tests of 15 min duration for each of four constant work rates, corresponding to 90% of the anaerobic threshold (AT) and 25, 50, and 75% of the difference between maximum VO2 (VO2 max) and AT for that subject. Time courses of VO2, minute ventilation (VE), and rectal temperature were recorded. Blood lactate, norepinephrine, and epinephrine were measured at the end of exercise. Eight weeks of cycle ergometer endurance training improved average VO2 max by 15%. Subjects then performed four tests identical to pretraining studies. For the above AT tests, training reduced VO2 drift substantially; reduction in each of the possible mediators we measured was also demonstrated. The training-induced decrease in VO2 drift was well correlated with decreases in end exercise lactate and less well correlated with the drift in VE seen at above AT work rates. The training-induced reduction in VO2 drift was not significantly correlated with attenuation of rectal temperature rise or decrease in end-exercise level of the catecholamines. Thus the slow rise in VO2 during heavy exercise seems linked to lactate, though a component dictated by the work of breathing cannot be ruled out.