The ventilatory response to exercise was determined in seven normal adults during induced chronic metabolic acidosis, chronic metabolic alkalosis, and a control state. Incremental and constant-load exercise tests were performed in each condition on a cycle ergometer. Ventilation and gas exchange variables were determined breath by breath, and CO2 partial pressure (PCO2), pH, and HCO3 were determined from arterialized venous blood (Pa-VCO2). During chronic metabolic acidosis PaVCO2 was lower than control (36.3 +/- 2.1 and 43.7 +/- 2.9 Torr, respectively) and during alkalosis it was elevated to 47.1 +/- 1.3 Torr. The new PCO2 levels caused by chronic acid-base alterations were unchanged during moderate exercise. The ventilatory response (VE) to the same metabolic rate increment was therefore larger (delta VE = 20.6 +/- 2.91/min) when PCO2 was lower than the control level (delta VE = 14.5 +/- 2.01/min. VE also increased more steeply in response to incremental exercise tests when PCO2 was reduced. Thus the hyperpnea of moderate exercise reflects the level at which arterial PCO2 is regulated at rest, as well as the metabolic load (VCO2).