Extracorporeal membrane oxygenation (ECMO) is used for long-term support of patients with acute respiratory failure. We investigated the effect of partial venoarterial (VA) and venovenous (VV) bypass with filler-free silicone spiral-coil membrane lungs on steady-state lung transcapillary fluid filtration in six unanesthetized lambs for periods of 11 to 32 hours. Using three thoracotomies we prepared animals to collect lung lymph; lymph obtained in this way is representative of lung interstitial fluid. By studying lymph flow and composition we demonstrated that the permeability of the pulmonary capillaries does not change during prolonged partial VV or VA bypass with a membrane lung. There was no accumulation of lung water during bypass, and lung protein and fluid leak neither increased not decreased with bypass flows equivalent to those used clinically. Thus prolonged use of ECMO in unanesthetized lambs appears to be neither harmful nor beneficial to the steady-state dynamics of fluid exchange in the lung. Furthermore, total pulmonary blood flow is not a determinant of net fluid filtration across the lung microcirculation.