Periodic respiration with pronounced apneas, produced by marked occlusion of cerebral blood vessels, was studied [in dogs]. The blood flow to the brain was curtailed by various methods. Increasing curtailment of blood flow was accompanied by initial stimulation of respiratory movements, followed by a period of partial or complete depression. After this depression, periodicity of ventilation sometimes followed. The periodicity of ventilation thus established was accompanied by periodic changes in mean blood pressure, volume flow of blood, and heart rate. The respiratory groups were initiated during decreasing flow of blood and decreasing blood pressure. In some experiments they terminated in apnea while blood pressure and blood flow were still decreasing and in others they extended for a short period into the increasing blood pressure and increasing blood flow. Since apnea was initiated towards the close of decreasing blood flow or beginning of increasing blood flow, it was suggested that apnea was produced by both severe depression and by processes of recovery. Accordingly apneas were designated as depression and recovery apneas. In experiments in which periodic changes in heart rate occurred, slowing of the heart was in the main associated with decreasing mean blood pressure and decreasing flow of blood, and augmentation with increasing blood pressure and increasing flow of blood. It is thus suggested that the cardio-inhibitory center is stimulated like the respiratory center by the same chemical mechanism. It was suggested that the rapid rate and gross change in chemical state of the medullary centers coupled with their impaired functional activity provide conditions for periodic activity. A decreased blood flow brings about a decrease in the chemical and physical transport of acid, a decrease in oxidations with a consequent broken coordination of the dual function of hemoglobin all resulting in an altered state of oxidations, and increased acidity of the respiratory center and an over ventilation of the blood. An increased blood flow of oxygenated blood now reverses these processes. Oxidative and non-oxidative removal of lactic acid and the liberation of free base and improved transport of acid combine to bring about a new state of oxidation and a decrease in acidity. The absence of changes in heart rate in 1 series of experiments with marked periodicity of ventilation, blood pressure, and blood volume flow indicates that periodicity may have its origin in periodic changes of the vasomotor center. However, the volume flow of blood ran parallel in the splanchnic, femoral, submaxillary, and cerebral blood vessels. Direct evidence of active vasomotor changes was, therefore, not obtained. These results suggest that periodic chemical stimulation of the circulatory centers produces periodic changes in ventilation of a central chemical origin. Since decreasing blood pressure may reflexly stimulate pulmonary ventilation this phenomenon may be looked upon as a possible modifying factor.