Psychosocial job stress has been shown to be associated with the development of cardiovascular disease. However, the pathophysiological mechanisms underlying this relationship remain unclear. The aim of the present study was to elucidate whether marked job stress affects the parameters of blood coagulation and fibrinolysis, such as plasma fibrinogen concentration, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) activities, in 213 middleaged male workers in a computer-producing factory. Job stress was measured using a Japanese version of the Job Content Questionnaire (JCQ) developed by Karasek. The mean t-PA activity in workers with lower and higher job demands was 0.23 and 0.18 IU/ml respectively, and this difference was significant (P < 0.05). The mean plasma fibrinogen in workers with lower and higher job decision latitude was 224.8 and 236.3 mg/dl respectively, and the mean PAI-1 activity in workers with lower and higher job strain was 14.9 and 17.7 U/ml respectively, though these differences remained at a borderline level of significance (0.05 < P < 0.10). Multiple regression analyses showed that the parameters of blood coagulation and fibrinolysis were closely associated with the cardiovascular risk factors of age, obesity, blood pressure, elevated serum lipids, and smoking, but that high job demands were significantly related to decreases in t-PA activity, independently of the traditional risk factors. These results suggest that psychosocial job stress may be related, at least partly, to the development of cardiovascular disease via changes in plasma fibrinolytic activity.