This study explored the relationship between clotting activation and tissue plasminogen activator and its inhibitor in cirrhotic patients with different degrees of liver failure. Sixty-seven patients (40 men, 27 women; age = 31-77 yr) with cirrhosis diagnosed by liver biopsy were divided into three subgroups (A, B and C) on the basis of Child-Pugh classification. Tissue plasminogen activator antigen and activity, plasminogen activator inhibitor antigen and activity, fibrin/fibrinogen degradation products, and D-dimer were measured in each patient. Forty-two patients with normal levels of fibridfibrinogen degradation products and D-dimer showed significant progressive decreases of plasminogen activator inhibitor antigen levels (p < 0.01) and activity (p < 0.0001) from class A to class C. This decrease was significantly related to prothrombin time (p < 0.003). Tissue plasminogen activator values were not different in the three Child classes. Twenty-five patients (7 class B and 18 class C) with high circulating values of fibridfibrinogen degradation products and D-dimer had higher values of tissue plasminogen activator antigen (20.0 2 10.1 ng/ml vs. 5.9 f 3.0 nglml; p < 0.0001) and activity (6.9 f 2.2 U/ml vs. 2.1 f 1.3 U/ml; p < 0.0001) and lower values of plasminogen activator inhibitor antigen (6.9 f 4.1 ng/ml vs. 14.8 f 5.6 ng/ml; p < 0.0001) and activity (4.1 2 2.8 U/ml vs. 9.8 f 3.7 U/ml; p < 0.0001) than did patients with normal values of fibrinlfibrinogen degradation products and D-dimer. We conclude that cirrhotic patients without systemic signs of hyperfibrinolysis exhibited progressive decreases of plasminogen activator inhibitor levels, suggesting that its blood levels are strongly related to liver function. The