Respiratory responses, measured from phrenic nerve activity, to stimulation of limb muscles or their afferent nerves were studied in anesthetized cats with intact brains, after cerebellectomy or decortication, and in unanesthetized decerebrate animals. All were vagotomized, glomectomized and paralyzed. Body temperature and end-tidal PCO2 were kept constant with servocontrollers. Nerve or muscle stimulation in animals with intact brains caused an increase in respiration which was followed by a respiratory afterdischarge, both of which have been described previously. In addition, stimulation of either muscle or nerve in animals with intact brains caused a post-stimulation depression of respiration that persisted for up to an hour. Decerebrated animals or those with spinal cord transection at cervical, thoracic or lumbar levels did not develop the response. In decorticated or decerebellated animals, the magnitude of the prolonged inhibition was markedly decreased. We conclude that: (1) stimulation of limb muscles or their afferent nerves activates a central neural mechanism which causes a prolonged depression of respiration; (2) the afferent input involved in this response is transmitted to the brain via spinal cord pathways; and (3) the cerebellum and suprapontine brain are required for full development of the post-stimulation inhibition.