Experiments were designed to test two hypotheses regarding the influence of isocapnic hypoxia on the expiratory activity of the abdominal muscles: 1) brain hypoxia attenuates the increased drive to the abdominal muscles that is elicited by hypoxic stimulation of peripheral chemoreceptor afferents, and 2) activation of the abdominal muscles in hypoxia requires vagal afferent feedback. The measurements included inspired ventilation (VI) and the electromyogram (EMG) of the external and internal oblique and transversus abdominis muscles in 12 supine cats that were anesthetized with chloralose (50 mg/kg) and breathed spontaneously. Changes in respiratory drive were evoked with isocapnic hypoxia or electrical stimulation of a carotid sinus nerve. Although both stimuli increased abdominal motor output, carotid sinus nerve stimulation evoked a significantly greater increase in the external and internal oblique EMG than hypoxia when comparisons were made at an equivalent level of VI. Neither stimulus changed the abdominal EMG significantly after bilateral cervical vagotomy. Separate experiments revealed that, at a given level of VI, hypercapnia evoked a significantly greater increase in abdominal activity than isocapnic hypoxia. The results suggest that the increased drive to the abdominal muscles elicited by stimulation of the peripheral and central chemoreceptors can be antagonized by an inhibitory input that is triggered by brain hypoxia. Moreover the decrease in expiratory motor activity often observed during hypoxia in vagotomized animals is due to the removal of an excitatory mechanism that is mediated by vagal afferent feedback.