Background: This study investigated the influence of domestic responsibility and job strain, and especially simultaneous exposure to these factors (i.e. ‘double exposure’) on common physical and mental symptoms in Swedish women. Methods: A questionnaire containing items on socio-economic factors, domestic responsibilities, and psychosocial working conditions was sent to a random population of women, 40 to 50 years of age, in a rural Swedish community. The response rate was 81.7% (397 women). Multiple logistic regression analyses were used to test for potential confounding factors and effect modification. Attributable risks were computed based on prevalence data. Results: Women shouldering great domestic responsibility or who experienced job strain were at risk of a high level of common symptoms (OR 1.76; 1.04–2.97 and OR 3.48; 2.05–5.92, respectively). ‘Double exposure’ considerably increased the odds for common symptoms (OR 6.91; 2.58–18.48), with support for synergy noted. The population attributable risk (PAR) of great domestic responsibility was 10.0% and of job strain it was 26.7% in producing a high level of common symptoms. The corresponding figure for the population of women subjected to ‘double exposure’ was 11.8% and for the population of women subjected to either single or ‘double exposure’ the PAR was 30.3%. Conclusion: Heavy domestic responsibility and/or a job strain situation are factors that seem to make important contributions to the causes of a high level of common symptoms among salaried women 40 to 50 years of age. ‘Double exposure’ showed a particularly high risk because of synergy.