Extrapulmonary support in respiratory failure has become possible for prolonged periods with clinical application of the membrane lung oxygenator. The membrane lung may be perfused in a venovenous circuit, in which case it functions by prepulmonary venous oxygenation, or it may be pumped in venoarterial perfusion as partial or total cardiopulmonary bypass. Four patients were placed on venovenous membrane lung (GE-Peirce) perfusion for periods ranging from 6 to 112 hours. In oxygenating blood flows of less than 50% of the cardiac output, a viable PaO2 (mean, 52 mm Hg) was obtained in 2 patients with 60% FIO2, including 1 survivor who was weaned from the membrane lung. The remaining 2 patients had heart failure and insufficient venovenous membrane lung flows to improve systemic oxygenation (mean PaO2, 45 mm Hg on 100% FIO2). Four other patients were placed on venoarterial membrane lung (GE-DuaLung) bypass for 18 to 110 hours. With 40 to 85% of the cardiac output bypassed through the membrane oxygenator, immediate improvement was seen in systemic oxygenation (mean PaO2, 75 mm Hg), effective compliance (mean increase of 75%), and reduction in pulmonary hypertension (mean decrease, 15 mm Hg). These changes during bypass allowed the lungs to be put at rest with a decrease in FIO2 and positive end-expiratory pressures. This clinical experience indicates that venoarterial membrane lung bypass may be both supportive and therapeutic, decompressing the pulmonary circuit and maintaining systemic oxygenation. Membrane lung supported by either mode of perfusion has been shown to be clinically effective in patients suffering acute respiratory failure.