OBJECTIVE In line with Karasek's job strain model, the objective of the study was to determine whether workers submitted to high job strain, a combination of high psychological demand and low decision latitude, develop more psychological distress than workers not submitted to high job strain. A second objective was to determine whether social support at work modifies the association between job strain and psychological distress. METHODS The design was cross-sectional and included white-collar workers in the Québec city area. A self-administered 26-item questionnaire (the Job Content Questionnaire) measured psychological demand, decision latitude, and social support at work. Psychological distress was measured by the Psychiatric Symptom Index, a 14-item self-administered instrument. RESULTS Among the 2889 participants, the prevalence of psychological distress was 27.8%. High job strain was present in 20.5% of the subjects. The crude odds ratio (OR) of high job strain with psychological distress was 3.52 [95% confidence interval (95% CI) 2.54-4.88]. The OR adjusted for age, gender, employment status, occupation, social support at work, nonwork social support, cynicism, hostility, domestic load, and stressful life events during the last 12 months was still significant (OR 2.45, 95% CI 1.66-3.62). CONCLUSIONS Our results support the association between job strain and psychological distress. Social support at work, although significantly associated with psychological distress, did not modify the association between job strain and psychological distress.