The endothelium appears to play an important role in the regulation of intravascular coagulation. Thrombomodulin is one of the anticoagulant substances that is expressed by endothelial cells. The influence of age and illness on the thrombomodulin-protein C system was studied prospectively in 80 cardiac surgery patients. Patients > 70 yr old (n = 20) were compared with patients < 50 yr (n = 20) (group I), and patients undergoing a simple cardiac procedure (n = 20) were compared with patients scheduled for complex surgery (n = 20) (group II). Thrombomodulin (normal < 40 ng ml(-1)), protein C and (free) protein S plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) after induction of anaesthesia (baseline values), during and after cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB and on the first day after operation. Blood loss and use of homologous blood and blood products were significantly greater in patients > 70 yr and in those undergoing complex surgery. At baseline, thrombomodulin con concentration was increased in patients undergoing complex surgery (mean 52 (SD 9) ng ml(-1)). After bypass and after operation, thrombomodulin increased most in patients > 70 yr (from 40 (8) to 78 (10) ng ml(-1)) and in those patients who underwent complex cardiac operations (from 52 (8) to 79 (10) ng ml(-1)) (P < 0.05). Changes in protein C and protein S concentrations were similar in all groups. On the first day after operation only, protein C concentrations were reduced in patients > 70 yr and in patients who underwent complex cardiac surgery. Older patients and those who underwent complex cardiac surgery had greater changes in the thrombomodulin-protein C system which may contribute to increased postoperative blood loss.