Thrombomodulin-dependent activation of endogenous TAFI in normal baboon plasma (NBP) results in prolongation of clot lysis. Lysis times were determined for clots formed with one third NBP, in the presence (■) and absence (●) of 2 μM tick anticoagulant peptide (TAP) with increasing concentrations of thrombomodulin (0-60 nM). Inhibition of thrombin activation by TAP resulted in reduced activation of baboon TAFI (bTAFI) both in the absence and presence of thrombomodulin. Thrombin alone activates bTAFI, and this effect is enhanced with increasing concentrations of thrombomodulin, achieving saturation by 12.5 nM thrombomodulin.