The turnover of 125I-bovine prothrombin fragment 1 was studied in the rabbit. The t1/2 of the peptide in the intravascular compartment was 11.5 hours and this compartment accounted for between 7.9 and 14.4% of the injected radioactivity. The rest of the radioactivity was distributed between two compartments in the extravascular space. The injection of the peptide (10 mg/rabbit) was associated with a transient increase in the plasma concentration of prothrombin and of factor X, with maximum concentration of prothrombin between 40 and 66 hours from the injection and between 26 and 40 hours for factor X. It is concluded that the injection of fragment 1 in the rabbit induced a transient increase in the synthesis of the vitamin K-dependent proteins that is compensated for by an increased absolute catabolic rate. It is suggested that the prothrombin activation peptide serves as regulatory message which induces the subsequent restoration of the appropriate concentration of the vitamin K-dependent proteins.