(J Extra-Corpor. Technol. 20[1] pp. 19–23, 32 references, Spring 1988) Complement activation is known to occur in procedures where blood comes into contact with non-biological surfaces. We followed complement activation in 5 infants undergoing long term extracorporeal membrane oxygenation (ECMO). Duration of ECMO varied from 121 hours to 309 hours. Changes in plasma C3a, C4a, C5a, and serum CH50 levels where measured before, during, and after ECMO. Upon initiation of ECMO, plasma C3a levels increased significantly during the first 2 hours. This was followed by a steady decline to pre-ECMO levels within 24 hours. Serum whole complement, measured by CH50 units, dropped markedly by 10 minutes after initiation of ECMO, returning to pre-ECMO levels in 24 hours. Plasma levels of C5a (a factor with high affinity for neutrophils) did not change significantly; nor did plasma C4a (a factor produced via activation of the classical pathway) show significant changes. Chest X-ray images uniformly demonstrated the onset of dense pulmonary opacification during the first 24 hours of ECMO treatment. This condition slowly cleared and appeared normal at termination of ECMO. We conclude that current ECMO circuitry mediates complement activation in neonates, probably via the alternate pathway. Activation is primarily limited to the first hours of ECMO and is no longer evident after 24 hours.