Aims To investigate the relationship between fibrinogen and stressful work conditions, where perceived strain is defined by the simultaneous presence of high psychological demands and low control, according to Karasek's Demand/Control/(Social Support) model. Methods and Results A cross-sectional study was realized between 1994 and 1998 in 24 Belgian enterprises, on 16335 male and 5084 female middle-aged workers of different Belgian companies participating in the Belstress study. This study confirmed the well-documented bivariate relationship between plasma fibrinogen levels and gender, age, educational level, smoking, obesity, physical activity, alcohol consumption, total cholesterol, HDL-cholesterol, arterial hypertension and diabetes. No independent multivariate relationship was observed between job control, psychological job demands or social support at work and plasma fibrinogen, but after stratification a positive association ( P ≤0·05) was observed between psychological job demands and plasma fibrinogen for males in the lowest educational level. Moreover a positive statistically significant association between job strain and plasma fibrinogen was observed in males but not in females. After stratification for educational level this association remained significant for males especially in the lowest educational level ( P ≤0·001) and became significant for females in the middle educational level. Conclusions As suggested in our study and others, plasma fibrinogen could be one of the potential mediators explaining the relationship between job stress and coronary heart disease. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.