The distribution and rates of catabolism were determined for rabbit antithrombin III (AT) isoforms differing in affinity for heparin-agarose. After isolation from rabbit plasma by heparin-affinity chromatography, the very-high-affinity form, ATvh, was labelled with 131I, and its high-affinity congener, ATh, with 125I. The two forms were separated from free iodine by heparin-affinity chromatography, and then injected simultaneously into young recipient rabbits. The disappearance-of-plasma-AT-radioactivity data were fitted to three exponential equations, and the resulting constants were used to calculate fractional catabolic rates and the various pool sizes for ATh and ATvh. The fractions of plasma ATh and ATvh catabolized daily (j3) were 0.763 +/- 0.023 and 1.88 +/- 0.057 day-1 respectively. Average values of jT, the daily fractional catabolic rates for the total-body ATh and ATvh, were 0.2633 +/- 0.0113 and 0.3832 +/- 0.0211 day-1. The ratios, ATh/ATvh, of the sizes of the plasma, non-circulating vascular-associated and extra-vascular compartments were 0.593, 0.990 and 1.30. By using a previous estimate of a 9:1 ATh/ATvh ratio in rabbit plasma and the calculated compartment sizes, the calculated relative ratio of ATh to ATvh was 5.4:1 in the non-circulating vascular-associated compartment. The data fit a model of antithrombin III distribution and catabolism in which a pool of endothelial-cell heparin-like receptors is seen to mediate the transfer of the inhibitor from plasma to interstitium with catabolism serving as an alternative to this transport.