Investigation of the periodic crescendo-decrescendo alterations in tidal volume in Cheyne-Stokes respiration (CSR) has provided remarkable insight into the physiology of respiratory control. Many patients with periodic breathing have both cardiac and neurologic disease. Considerable controversy has surrounded determination of the relative importance of cardiac and neurologic mechanisms in the genesis of this breathing abnormality. Several investigators have considered the respiratory center as a chemostat model with three basic components: the controller system (chemoreceptors), the controlled system (gas tensions of O2 and CO2), and the feedback loop (arterial circulation from the lung to the brain). If the relationship between these cardiac and neurologic components is altered, stability of the respiratory control system is lost. Such disturbance in the control system may arise by prolongation of the circulation time, or by the system becoming more dependent on its O2, rather than the CO2 component. Earlier investigators considered periodic breathing as a forewarning of ominous developments. In recent studies, mild degrees of periodic breathing, easily missed on physical examination, are often found in otherwise normal subjects, particularly during sleep. Generally no therapy is required, although aminophylline, O2 or CO2 administration has been shown to abolish periodic breathing.