Plasma leakage through microporous membrane oxygenators is a well known complication of prolonged extracorporeal circulation. The authors hypothesized that adsorption of bipolar plasma molecules, such as phospholipids on the microporous membrane, results in formation of a hydrophilic layer over the hydrophobic surface of the membrane; this, in turn, leads to plasma leakage at normal surface tensions. A lipid phosphorus assay was used to measure phospholipid adsorption onto the fibers of microporous membrane oxygenators tested under a variety of experimental conditions. Adsorption of phospholipids on the microporous membrane was concentration dependent. Reproducible plasma leakage occurred both in vitro and in vivo, and the time to leakage was dependent on the concentration of phospholipids adsorbed upon the microporous membrane. Based upon these results, the authors conclude that adsorption of phospholipids contributes to the development of plasma leakage through microporous membrane oxygenators.