Using the demand-control-support model of job strain, the authors examined gender differences in the relationship between psychosocial work exposures and psychological distress in a cross-sectional sample of 7,484 employed Canadians. Compared with low-strain work, high-strain and active work were associated with a significantly higher level of distress in both men and women. Differences in psychological distress in relation to psychosocial work exposures were greater for men than for women. Low social support was associated with higher distress across all categories of job strain, and the combined effect of low social support and high job strain was associated with the greatest increase in distress. This pattern was similar in men and women. This study suggests that psychosocial work exposures may be a more significant determinant of psychological well-being in male workers compared with female workers.