We studied ventilation and inspiratory muscle activity during progressive isocapnic hypoxia in adult asthmatic patients to determine whether the decreased hypoxic ventilatory response previously identified is due to the mechanical abnormalities of the respiratory system or to low respiratory center output. The mouth pressure produced by inspiratory muscle activity, a reflection of respiratory center output, was measured at 100 msec of inspiration against an occluded airway at functional residual capacity. At end-tidal oxygen tension (PETO2) of 80 mm Hg, inspiratory muscle activity was greater in asthmatic patients than in normal subjects for the same level of ventilation, but at PETO2 of 40 mm Hg, both inspiratory muscle activity and ventilation were lower in asthmatic patients. Consequently, the changes in inspiratory muscle activity and ventilation per mm Hg change in PETO2 were lower in the asthmatic patients. To generate the same ventilation during progressive hypoxia, more inspiratory muscle activity was needed by asthmatic patients. We concluded that the decreased hypoxic ventilation in asthmatic patients resulted from both decreased respiratory center output and from mechanical abnormalities of the respiratory system.