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Background As a first step toward the development of an artificial placenta, we investigated the relationship between blood flow rate through an arteriovenous (A-V) circuit/oxygenator and both CO 2 elimination and hemodynamic stability in a small animal model. Methods Male New Zealand rabbits (N = 10) with an average weight of 2.7 ± 0.2 kg were anesthetized, paralyzed, and heparinized before carotid-jugular cannulation. A tracheostomy tube, an arterial catheter, and an aortic flow probe were placed. Arteriovenous flow through a custom-made, low-resistance, 0.5 m 2 hollow fiber oxygenator was initiated. Oxygen sweep flow was maintained at 300 mL/min, whereas blood flow was controlled at 10 to 40 mL/(kg min). Ventilation was discontinued during each blood flow rate trial. Hemodynamic and preoxygenator and postoxygenator blood gas data were recorded 30 minutes after initiation of each flow rate. CO 2 removal was the product of the oxygen sweep gas flow rate and the sweep flow exhaust CO 2 content as determined by capnometry. Data were analyzed by analysis of variance with post hoc Dunnett's t test. Results CO 2 removal increased and Paco 2 decreased as a function of A-V blood flow rate. Simultaneously, systolic blood pressure did not significantly change. CO 2 removal was effective at device flows greater than 20% of cardiac output. Conclusion In this rabbit model, A-V blood flows at 25% to 30% of cardiac output allow full gas exchange without hemodynamic compromise. This model raises the possibility of using A-V support and an artificial placenta in newborns with respiratory failure.