In the human circulation, factor VII is present in relatively low plasma concentration (0.01 µM) and has been reported to have a short half-life (t_1/2; 6 h). In contrast, prothrombin is present in a relatively high plasma concentration (2 µM) and has a relatively long catabolic half-life (t_1/2 = ~2-3 days). This report examines the metabolic characteristics of purified rabbit plasma factor VII and prothrombin, radiolabeled with ¹²⁵I and ¹³¹I, respectively, in healthy young rabbits. From the plasma clearance curves of protein-bound radioactivities, fractional catabolic rates and compartmental distributions were calculated using a three-compartment model. Turnover of factor VII within the intravascular space (2.95 days) exceeded that of prothrombin (1.9 days). However, the whole body fractional catabolic rate of factor VII (0.34 days¹; catabolic t_1/2 = 2.04 days) was significantly slower than that of prothrombin (0.53 days¹; t_1/2 = 1.31 days). Furthermore, the fractional distributions of factor VII in the intravascular (0.14) and extravascular compartments (0.76) differed from those of prothrombin (0.29 and 0.53). Absolute quantities of factor VII and prothrombin catabolized by a 3-kg rabbit amounted to 0.18 and 24.0 mg/day, respectively (molar ratio of prothrombin to factor VII = 100). The molar ratio of catabolism was compared with the release rates of factor VII and prothrombin from rabbit livers perfused ex vivo. After correction for uptake of factor VII and prothrombin by the liver, the molar ratio of released prothrombin to factor VII in the perfusate was ~293:1 over a 0.25- to 3-h interval. These results indicate that, compared with prothrombin, factor VII in the healthy rabbit circulates as a relatively long-lived protein. This behavior does not reflect that reported for factor VII in the human circulation.