BACKGROUND: Work stress has become a major occupational risk factor in industrialized countries and an important economic issue. The objective was to estimate the annual costs of coronary heart diseases (CHD) and mental disorders (MD) attributable to job strain exposure according to Karasek's model in France for the year 2003 from a societal perspective. METHODS: We produced attributable fraction estimates which were applied to the number of cases (morbidity and mortality) and the costs of CHD and MD. Relative risk estimates came from a systematic literature review of prospective studies. We conducted meta-analyses based on this selection of studies. Prevalence of exposure to job strain came from the national SUMER survey conducted in France in 2003. Costs included direct medical costs and indirect costs: production losses due to sick leaves and premature deaths. RESULTS: Between 8.8 and 10.2% of CHD morbidity was attributable to job strain, and between 9.4 and 11.2% of CHD mortality was attributable to this exposure for men. Between 15.2 and 19.8% of MD was attributable to job strain for men, and between 14.3 and 27.1% for women. As a whole, between 450 000 and 590 000 cases of diseases and 910--1130 deaths were attributable to job strain for men. From 730 000 to 1 380 000 cases of diseases and from 150 to 280 deaths were attributable to job strain for women. The total number of sick leave days amounted from 5 to 6.6 million days for men, and from 8.5 to 16 million days for women. The total costs of CHD and MD attributable to job strain exposure ranged from 1.8 to 3 billion euros for the year 2003 (0.12-0.19% GDP). Medical costs accounted for 11% of the total costs, value of life costs accounted for 13-15% and sick leave costs for 74-77%. The cost of CHD was estimated at 113--133 million euros and the cost of MD was between 1.7 - 2.8 billion euros in 2003. CONCLUSION: This study on the economic burden of diseases attributable to job strain in France provides relevant insights for policy-makers when defining public health priorities for prevention policies.