To define the roles of mechanical loading, respiratory neuromuscular control, and sleep apnea in the pathogenesis of obesity hypoventilation, respiratory muscle drive and output, assessed by diaphragmatic electromyogram (EMGdi) and mouth occlusion pressure (P0.15), respectively, were determined during CO2 chemostimulation in nonobese volunteers who were subjected to abdominal mass loading, and in three groups of markedly obese patients: eucapnic obese without sleep apnea (O), eucapnic obese with sleep apnea (OSA), and hypercapnic obese with sleep apnea (OH). The P0.15 responses were decreased in OSA and OH, but the EMGdi responses were not significantly different from those in control subjects. In O patients EMGdi responses were significantly greater than those in control subjects as well as those in OSA and OH patients. EMGdi and P0.15 responses increased in all nonobese subjects when they were subjected to mass loading. We conclude that both OSA and OH patients were equally unable to develop the expected increase in respiratory muscle drive and output. The presence of sleep apnea, possibly by causing nocturnal hypoxemia and/or sleep fragmentation, may result in impaired mass load compensation and predispose obese patients to develop hypercapnia.