Variable hemodynamic responses to positive end-expiratory pressure (PEEP) with spontaneous ventilation have been reported. To clarify these responses, 15 awake patients were studied using a catheter-tip velocity transducer to record phasic aortic root blood flow continuously before, during and after PEEP (10 cm H2O) applied with a face mask. Central blood volume and effective ventricular filling pressures were measured. Phasic pulmonary artery blood flow was also simultaneously recorded in three of these patients. PEEP produced an acute aortic blood flow reduction, detected within one respiratory cycle. Stroke volume decreased 12%, and since heart rate was unchanged, cardiac output also declined (p less than 0.05). Inspiratory-to-expiratory aortic flow changes were less during PEEP. In contrast, inspiratory-to-expiratory pulmonary artery flow alterations were exaggerated due to a marked flow decline during expiration. Central blood volume and effective left ventricular filling pressure decreased 9% and 19%, respectively (p less than 0.05 in all patients). The decrease in pulmonary artery flow was associated with a decrease in central blood volume in the three patients in whom pulmonary flow was measured. PEEP promptly reduces cardiac output during spontaneous ventilation, related to a decrease in pulmonary flow in expiration.