Although minute ventilation (VE) exhibits marked increases during heavy rhythmic exercise utilizing a large muscle mass, the extent to which this hyperpnea stresses the respiratory muscles remains controversial. In an attempt to resolve this matter, we measured arterial blood lactate concentration during seated isocapnic reproduction of peak exercise ventilation. This level of ventilation had previously been identified during a maximal 2-min treadmill run. We found that maintenance of peak exercise ventilation raised blood lactate 50% in subjects otherwise at rest (N = 8, P less than 0.01). This lactate rise occurred despite addition of CO2 to inspired gas in amounts sufficient to maintain arterial blood pH and PCO2 at resting levels, which suggests that achieving the high exercise ventilation associated with VO2max may require significant anaerobic metabolism by respiratory muscles.