Although periodic breathing consisting of alternating hyperpnea and hypopnea has been recognized in heart failure patients, its mechanism has not been clarified. We hypothesized that heart failure patients who have oscillations in ventilation will also be found to have oscillations in pulmonary blood flow, as reflected in left ventricular ejection fraction. To test this hypothesis, we analyzed continuously gas exchange and left ventricular ejection fraction during exercise in cardiac patients who exhibited periodic breathing. Out of 48 consecutive patients with reduced left ventricular function who performed a symptom-limited incremental exercise test using an upright cycle ergometer, we selected 5 patients who exhibited clear ventilatory oscillations during exercise. These patients repeated the same exercise test on another day for measuring gas exchange and left ventricular ejection fraction continuously. Oscillatory changes were noted both in left ventricular ejection fraction and in ventilation in these patients. These observations offer support for the hypothesis that fluctuations in pulmonary blood flow are primarily responsible for the periodic breathing seen in heart failure patients.