The intravascular oxygenator/carbon dioxide removal device (IVOX) is a hollow fiber, implantable membrane oxygenator that lies in the vena cavae and is designed to augment gas exchange during acute respiratory failure. An ovine model of smoke inhalation injury (lethal dose for 50% of animals at 48 hr) was used in eight ewes to test the safety and efficacy of this device. The IVOX was placed in the vena cavae through a right internal jugular vein cut-down. A vacuum pump withdrew O2 through the hollow fiber membrane, and IVOX gas flow was measured with a flow meter. Outlet gas was analyzed for CO2 concentration. Changes in O2 exchange were calculated as changes in mixed venous O2 content with the IVOX on compared with the IVOX off, multiplied by the cardiac output. The IVOX did not significantly change cardiac output, mean arterial pressure, pulmonary artery pressure, or hemoglobin concentration measured every 6 hr for 48 hr. The maximum CO2 exchange averaged 40.2 +/- 10.5 ml CO2/min. The average change in oxygen exchange was 98.4 +/- 76.0 ml O2/min. Iliac vein injury from attempted IVOX placement without fluoroscopic guidance resulted in one death. The authors concluded that the IVOX was safe when properly inserted and provided approximately 25-30% of the gas exchange requirements in this model.