Effects of estradiol, progesterone, cortisol, thrombophlebitis and typhoid vaccine on the synthesis and catabolism of antithrombin III (AT) in dogs were studied, using I-125-labeled AT (I-125-AT) as a tracer. Five dogs were used for each study. A single intramuscular injection of 20 mg estradiol caused a 20% decrease of plasma AT concentration in 6 days without appreciable changes in the plasma half-lives of I-125-AT but with a significant decrease in the fractional catabolic rate of I-125-AT(j3u). A single intramuscular injection of 250 mg progesterone did not produce any appreciable changes of plasma AT concentration, the plasma half-lives of I-125-AT or j3u. On the other hand, intravenous and intramuscular injections of a total of 750 mg cortisol caused a 17% increase of plasma AT concentration in a day after the injections without alterations of the plasma half-lives of I-125-AT or j3u. Next, thrombophlebitis was produced in dogs by a single intravenous injection of 1 ml 90% phenol into a leg vein occluded for 1 min by a gauze tourniquet and the effects of thrombophlebitis were studied. The results indicated that it did not cause appreciable changes of plasma AT concentration, the plasma half-lives of I-125-AT or j3u. However, studies of the effects of a single intravenous injection of 3 ml typhoid vaccine showed a 25% decrease of plasma AT concentration in a day after the injection with a moderate acceleration of the decline rate of plasma I-125-AT and a 14% increase in j3u values. Further studies in heparinized dogs showed similar effects with typhoid vaccine. These results indicate that estradiol causes a decreased rate of AT synthesis, that progesterone has no appreciable effects on AT metabolism, that cortisol increases the rate of AT synthesis, that localized thrombophlebitis has no appreciable effects on AT metabolism and that typhoid vaccine causes an increased j3u by unknown mechanisms which is not an accelerated coagulation process.