Serious thrombotic complications occur in sick neonates, while healthy infants have a very low risk of thrombosis. To better understand the regulation of physiological anticoagulation at birth, components oftheprotein C pathway weremeasured in cordplasma samples from 14 full-term healthy newborns and in samples from 10 adult controls. Although zymogen protein C was significantly reduced in cord plasma (mean ± SEM in cord vs. adult samples 37 ± 1.4% vs. 90 ± 5.5%, p < 0.0001), levels of the active enzyme, activated protein C (APC), were not (119 ± 20% vs. 75 ± 12%, p = 0.0762) Relative to the protein C level, cord plasmas had a 5.2-fold higher APC level (p < 0.01). The A PC increase was partially due to slower inactivation of A PC in cord plasma (half-life for APC 50 min in cord plasma vs. 27 minutes in adult plasma). Increased sensitivity of factor V to inactivation by APC in cord plasma was observed since the activated partial thromboplastin time-based A PC sensitivity ratio was significantly increased for cord vs. adult plasma samples (2.28 ± 0.09 versus 1.97 ± 0.03, p < 0.01). Thus, despite low zymogen protein C, the protein C pathway in newborns seems to be functionally well developed and at an activated stage at birth.