Twenty-five preterm newborns were given bolus infusions of sodium heparin (100 units/kg) and plasma heparin levels were assayed at 5, 20, 40, 90, and 150 min. Eight normal adults received a 75 units/kg bolus of heparin and levels were assayed at 5, 30, 60, 120, 180, and 240 min. In comparison with the adult data (mean adult plasma heparin half life (T1/2) = 63.3 min), the newborn infants demonstrated a significantly shorter plasma heparin half life (T1/2 = 35.5 min in group I, 33 to 36 wk gestation; 35.5 min in group II, 29 to 32 wk gestation; and 41.6 min in group III, 25 to 28 wk gestation), as demonstrated by a chromogenic heparin assay. The newborn groups, had a larger volume of distribution (Vd) of heparin which varied inversely with gestational age (Vd =36.6 ml/kg in the adults, 57.8 ml/kg in group I, 73.3 ml/kg in group II, and 81.0 ml/kg in group III babies. Heparin clearance (CI) was significantly greater in all newborn groups when compared with the adult (CIadult = 0.43 ml/kg/min; ClGrIII = 1.49 ml/kg/min). A one-stage clotting assay for heparin generated similar results, although infant plasma heparin levels were slightly higher by this assay. Before heparin administration, the mean antithrombin III antigen (AT-III Ag) of the babies was 26.5% of normal adult and was not furthur decreased 90 min after the heparin bolus.