To study factor VII (F VII) hyperactivity in chronic dialysis patients, we measured the plasma levels of F VII activity (F VII c) and antigen (F VII Ag), prothrombin activation fragments 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and thrombomodulin in 28 patients on hemodialysis. Marked elevation of F VII c was found in long-term dialysis patients (185 +/- 30%). This hyperactivity was accompanied by both elevation of the F VII Ag level (153 +/- 28%) and enhanced activation of F VII zymogen, expressed as the F VII c/F VII Ag ratio (1.23 +/- 0.23), but pseudocholinesterase activity was decreased. The 6 patients with ischemic heart disease had slightly higher F VII c (200 +/- 25%) than those without ischemic heart disease (181 +/- 30%), although the difference was not significant. Increased F VII c was accompanied by factor Xa hyperactivity (a high plasma F1 + 2 level) in the long-term dialysis patients, but there was no significant elevation of plasma TAT levels when compared with controls matched for age, sex, and the presence or absence of diabetes mellitus. Plasma TAT levels were significantly correlated with plasma thrombomodulin levels, suggesting that thrombin generation in blood as a result of hemodialysis could induce systemic endothelial cell injury.