We tested the hypothesis that prior heavy-intensity exercise reduces the difference between asymptotic oxygen uptake (VO2) and maximum oxygen uptake (VO2max) during exhaustive severe-intensity running lasting »2 minutes. Ten trained runners each performed 2 ramp tests to determine peak VO2 (VO2peak) and speed at ventilatory threshold. They performed exhaustive square-wave runs lasting »2 minutes, preceded by either 6 minutes of moderate-intensity running and 6 minutes rest (SEVMOD) or 6 minutes of heavy-intensity running and 6 minutes rest (SEVHEAVY). Two transitions were completed in each condition. VO2 was determined breath by breath and averaged across the 2 repeats of each test; for the square-wave test, the averaged VO2 response was then modeled using a monoexponential function. The amplitude of the VO2 response to severe-intensity running was not different in the 2 conditions (SEVMOD vs SEVHEAVY; 3925 ± 442 vs 3997 ± 430 mL/min, P = .237), nor was the speed of the response (t; 9.2 ± 2.1 vs 10.0 ± 2.1 seconds, P = .177). VO2peak from the square-wave tests was below that achieved in the ramp tests (91.0% ± 3.2% and 92.0% ± 3.9% VO2peak, P < .001). There was no difference in time to exhaustion between conditions (110.2 ± 9.7 vs 111.0 ± 15.2 seconds, P = .813). The results show that the primary VO2 response is unaffected by prior heavy exercise in running performed at intensities at which exhaustion will occur before a slow component emerges.