Thrombomodulin (TM) is a membrane protein present in the vascular endothelium. It has also been found in human plasma, within which, however, its pathological functions have not been clearly described. In this study, the plasma TM concentrations in 19 asthmatic patients were determined by sandwich enzyme immunoassay using two monoclonal antibodies for human TM. The concentration of plasma TM in exercise-induced asthma (EIA)-positive asthmatic patients was significantly increased by exercise challenge. In addition, for these patients a positive correlation was found between the severity of EIA and the degree of change in plasma TM induced by exercise challenge. These findings suggest that the increase in influx of TM into the plasma in EIA-positive asthmatics may be due to generalized pulmonary endothelial damage following exercise challenge.