Résumé : Working conditions and domestic situation have been proven to impact on men’s and women’s mental health. This study aims to evaluate whether disparities exist between men’s and women’s anxiety, chronic fatigue and subjective health, when taking into account the role played by isolated job strain (Karasek et al., 1998) and home-work interference – HWI - (Kelloway et al., 1999), as well as their interplay. Data result from the pooling of two large Belgian longitudinal studies (BELSTRESS III, SOMSTRESS) comprising 4810 workers (2847 women). We performed separately for both sexes logistic regressions setting as predictor a 4 levels variable resulting from the combination of the explanatory variables: low iso-strain and low HWI, high iso-strain and low HWI, low iso-strain and high HWI, and high iso-strain and high HWI. Moreover, data have been progressively adjusted for 4 blocks of variables: socio-demographical, work-, private life- and health-related variables. Results show that, when individuals experience HWI, but no iso-strain, there are little differences between males’ and females’ distress. On the contrary, when iso-strain occurs, but not HWI, men appear to be more affected than women. Finally, looking at the interaction, we found that while the accumulation of high iso-strain and high HWI affects women mainly on chronic fatigue, the same pattern has a stronger impact on men’s perceived health. In the future, given their implications for productivity, risks of accidents, or sick leave, investigations are needed to clarify the antecedents and consequences of the articulation between working and private life components.