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Clotting abnormalities are well-recognized complications that occur with high frequency in patients suffering from underlying malignant diseases. New and highly sensitive molecular markers of hemostasis, thrombin-antithrombin III complex (TAT III), D-dimer fragments (DD), and plasmin-α1-antiplasmin complex (PIC) were measured in 58 consecutive lung cancer patients. Significant elevation in the blood concentrations of DD, PIC, and TAT was found in lung cancer patients, with either extensive or limited disease compared with values obtained in a healthy control group and in another group of patients with chronic obstructive pulmonary disease. Patients with distant metastasis exhibited significantly higher levels of these parameters as compared to those without metastasis. These data indicated that there was a subclinical activation of blood coagulation and fibrinolysis in lung cancer from the early clinical stages of the disease. In addition, there appeared to be different levels of clotting activation according to histologic type of tumor and response to chemotherapy.