In 13 neonates undergoing cardiac operations for congenital cardiac defects, complement, leukocytes, and leukocyte elastase were studied during and after cardiopulmonary bypass. All but two neonates received prostaglandin E1 before the operation. The C3d/C3 ratio rose significantly during cardiopulmonary bypass from 0.86 +/- 0.55 to 1.40 +/- 0.56 (mean +/- standard deviation; p < 0.0001). Abnormally elevated C5a levels (18.6 +/- 7.3 micrograms/L) were measured at the end of cardiopulmonary bypass. C4 was not overtly consumed during the procedure. Leukocytes fell from a preoperative value of 10.06 +/- 3.15 x 10(9)/L to 3.21 +/- 0.64 x 10(9)/L after beginning of cardiopulmonary bypass (p < 0.0001) and rose at the end of the procedure from 2.33 +/- 0.67 x 10(9)/L to 7.19 +/- 1.84 x 10(9)/L, after protamine administration (p < 0.0001). Neutrophils fell from a preoperative value of 5.14 +/- 1.18 x 10(9)/L to 1.46 +/- 0.35 x 10(9)/L after beginning of cardiopulmonary bypass and rose at the end of extracorporeal circulation from 1.00 +/- 0.31 x 10(9)/L to 4.10 +/- 1.18 x 10(9)/L, after protamine administration (p < 0.005). Elastase release occurred in all neonates during cardiopulmonary bypass and averaged 331.5 +/- 175.7 micrograms/L. Complement activation and leukocyte stimulation did not correlate with postoperative complications or outcome. This study demonstrates complement activation and leukocyte stimulation in neonates undergoing cardiac operation.