1. The metabolism of human antithrombin III (ATIII) was studied by using 125 I-labelled tracer. 2. The plasma half-life ( t 0.5 ) was 2.71 ± 0.26 days in normal subjects and was similar in patients with cirrhosis or primary carcinoma of liver. 3. Patients with cirrhosis had low ATIII levels, decreased intravascular mass, total body mass and decreased absolute catabolic rate, suggesting decreased synthesis. The positive correlation of ATIII level with fractional catabolic rate ( K 10 ) indicated that the decreased catabolism might exert a positive inhibition on ATIII production. 4. These abnormalities were more exaggerated in patients with macronodular cirrhosis associated with hepatitis surface antigen or in those with ascites. 5. In cirrhotic patients with ascites an additional extravascular pool of ATIII was present which did not turn over at the same rate as the intravascular pool. 6. Patients with primary carcinoma of liver had moderately low ATIII, but normal intravascular mass and total body mass because of the increased plasma volume and normal absolute catabolic rate. 7. The negative correlation of ATIII levels with K 10 suggested that the low levels could be due to increased catabolism or consumption. 8. One patient with disseminated malignancy and active superficial thrombophlebitis had normal ATIII metabolism.