To elucidate the role of leukocytes in intravascular clotting in patients with septicemia, plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty out of 33 patients revealed a marked leukopenia (leukocyte count was less than 1,000/microliters) due to suppression of hematopoiesis by the administration of chemotherapeutic agents for the treatment of hematological malignancies. Thirteen out of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients with leukopenia were significantly lower than those in patients whose leukocyte counts were higher than 1,000/microliters. Plasma fibrinogen levels were significantly lower in patients whose leukocyte counts were higher than 1,000/microliters than those in patients with leukopenia. Plasma TAT levels were found to correlate well with the number of leukocytes in these patients with the correlation coefficient (R) of 0.67 (p less than 0.001). Significantly high positive correlation was observed between plasma TAT levels and the number of monocytes (R = 0.92, p less than 0.001). Significant correlation was also observed between plasma SFMC levels and the number of monocytes (R = 0.72, p less than 0.001). No significant correlation was found between the number of platelets and TAT levels. These findings suggest that leukocytes (especially monocytes) play a critical role in activating intravascular coagulation in septicemic patients.