Blood coagulation Factor Xa and activated protein C are both serine proteases derived from circulating, vitamin K-dependent precursors. They express, respectively, procoagulant and anticoagulant properties through Ca2+ and phospholipid-dependent interactions with coagulation Factor Va. The present studies were undertaken to determine whether Factor Xa and activated protein C interact independently or competitively with Factor Va. The interactions were assessed by examining the activated protein C-catalyzed inactivation of Factor Va in the absence and presence of Factor Xa at various concentrations. The results indicated that the two proteins compete for Factor Va and that Factor Xa protects Factor Va from inactivation by activated protein C. The ability of Factor Xa to protect Factor Va was observed either in the absence of a Factor Xa substrate or under conditions in which the complex of Factor Va and Factor Xa was engaged in the conversion of substrate (prethrombin 1) to thrombin.