The objectives are to examine if the excess risk of myocardial infarction from exposure to job strain is due to interaction between high demands and low control and to analyse what role such an interaction has regarding socioeconomic differences in risk of myocardial infarction. The material is a population-based case-referent study having incident first events of myocardial infarction as outcome (SHEEP: Stockholm Heart Epidemiology Program). The analysis is restricted to males 45-64 yr of age with a more detailed analysis confined to those still working at inclusion. In total, 1047 cases and 1450 referents were included in the analysis. Exposure categories of job strain were formed from self reported questionnaire information. The results show that high demands and low decision latitude interact with a synergy index of 7.5 (95% C.I.: 1.8-30.6) providing empirical support for the core mechanism of the job strain model. Manual workers are more susceptible when exposed to job strain and its components and this increased susceptibility explains about 25-50% of the relative excess risk among manual workers. Low decision latitude may also, as a causal link, explain about 30% of the socioeconomic difference in risk of myocardial infarction. The distinction between the interaction and the causal link mechanisms identifies new etiologic questions and intervention alternatives. The specific causes of the increased susceptibility among manual workers to job strain and its components seem to be an interesting and important research question.