The development of the human C′ system was studied by quantitation of total serum hemolytic C′ activity (C′H50) and the individual serum protein C′ components, C′3, C′4 and C′5, in premature and term neonates. It was found that term and premature newborns were deficient in C′H50, C′3, C′4 and C′5 as compared with their mothers and normal adults. In only one instance the neonatal concentrations of C′H50, C′3, C′4 and C′5 were greater than those in the maternal serum; in this instance mother had a marked deficiency of serum C′H50, C′3, C′4 and C′5. The ratios of term neonatal-to-maternal serum concentrations were: C′H50, 0.53; C′3, 0.54; C′4, 0.56; C′5, 0.61. The calculated maternal-neonatal correlation coefficients (r) were: C′H50, 0.61; C′3, 0.32; C′4, 0.50; C′5, 0.31. Serum concentrations of C′H50, C′3, C′4 and C′5 increased proportionally with gestational neonatal age and reached adult concentrations within 3 to 6 months of age. In general, the synthesis of C′3, C′4 and C′5 appeared to develop simultaneously and in sequence with total hemolytic activity (C′H50).