Regulation of blood coagulation was studied in 12 dogs, using subcutaneous administration of sodium heparin. Dosage of heparin needed to achieve the desired 1.5- to 2.5-fold increase in the activated partial thromboplastin time (APTT) was 250 to 500 IU/kg of body weight. Increased APTT lasted less than 6 hours. Repeated heparin administration, using the lowest dosage (250 IU/kg) every 6 hours, induced an unacceptable prolongation of clotting times during the first 2 days of treatment. Prolonged administration at a dosage of 200 IU/kg every 6 hours adequately maintained the desired hypocoagulative state initially; after 2 days, however, the prolonged APTT steadily decreased. The decreasing effect was proportionate to a decrease in plasma antithrombin III (AT III). To sustain a correctly balanced hypocoagulative state from prolonged subcutaneous administration of heparin, APTT values should be determined regularly to monitor therapy. In addition, transfusion of AT III-rich donor plasma may be necessary when low plasma AT III reduces the effects of heparin.