Pulmonary ventilation and pattern, arterial blood gases, and [H+] were studied in 15 highly trained runners [maximum O2 consumption (VO2 max) 53--82 ml . kg-1 . min-1] during road racing (24 km, n = 5) and 60--70 min of treadmill running (70--75% VO2 max, n = 13). The predominant response throughout prolonged treadmill running and especially road running was a tachypneic, respiratory alkalosis (-5 to -12 Torr PaCO2) that was evident early in the exercise. Time-dependent increases in breathing frequency (10--40%, 6--60 min work), expired ventilation, and dead space ventilation were common in prolonged work; these were especially evident in two subjects even as VO2 fell during road racing under hot humid conditions. The tachypneic hyperventilation was 1) most often accompanied by alkaline [H+]a, 2) associated with time-dependent elevation in rectal temperature (1--1.5 degrees C) and circulating norepinephrine (5--20 x rest), 3) quickly alleviated via hyperoxia after 60--70 min of exercise, and 4) was shown to result from increased running velocity in separate experiments that compared walking vs. running at similar CO2 excretion and [HCO-3]a. In highly trained runners competing under favorable environmental conditions and optional pace selection, we view the net effects of the hyperventilatory response to be truly advantageous, whereby the benefits to pulmonary gas exchange and [H+] regulation outweigh the expense of some inefficiency in ventilatory work and pattern and a departure from steady-state homeostasis.