We have determined the plasma concentrations of protein S and C4BP in 25 term and 26 preterm infants by radioimmunoassay. Both the total concentration and the concentration of free protein S were quantified. The concentration of C4BP was very low in preterm infants (mean 6% of the adult level). In term infants, the level had increased to a mean of 18%. Total protein S was decreased both in preterm and term infants, 4.0 mg/l and 6.8 mg/l respectively, as compared to the mean adult concentration, 20.6 mg/l. In preterm infant plasma, free protein S was the predominant (85%) form, probably due to the very low C4BP level. In plasma from term infants, free protein S represented 68% of the total protein S, the corresponding value in adult controls being 37%. The plasma concentration of free protein S in preterm and term infants was 3.3 mg/l and 4.6 mg/l, respectively (mean adult value 7.6 mg/l). These results demonstrate that, while the total protein S concentration in preterm and term infants was very low in comparison to the adult level, the difference in the concentration of the anticoagulant, active, free form of protein S between infants and adults was less pronounced.