Chronic liver disease is accompanied by derangement of hepatocyte function including the synthesis of haemostastic factors. It is, however, not known whether the improvement in liver functions as a result of interferon (IFN)-α therapy would be reflected in the plasma levels of these factors. To evaluate the effect of IFN-α therapy on the plasma levels of natural anticoagulants and on the fibrinolytic parameters, in patients with chronic viral hepatitis. Twenty one patients with chronic viral hepatitis (B and C) were treated with IFN-α, and were studied before commencement of therapy (first sample) 3 (second sample) and 6 months (third sample) later. The coagulation screening tests: activated partial thromboplastin time, prothrombin time, thrombin time, reptilase time and plasma fibrinogen and the natural anticoagulants: antithrombin, Protein C and free and total protein S as well as fibrinolytic parameters (tissue type plasminogen activator, plasminogen activator inhibitor type-1 and plasminogen) were measured. An increase in the levels of total protein S at 3 and 6 months after the commencement of IFN therapy was noted but the increase was statistically significant in the latter period. Reptilase time was prolonged in the first (pretreatment) and in the second samples and then began to decrease in the third sample but remained higher than the pretreatment level. Fibrinogen level increased in the second and third samples. No remarkable changes were noted in other haemostatic parameters. Total protein S level is a good marker of response to IFN therapy. IFN therapy does not affect other natural anticoagulants or fibrinolytic parameters. More detailed studies need to be done to confirm these findings.