The first phase of this longitudinal study consisted of a questionnaire completed by a cohort of 1,891 nurses (aged 23-65 years) from six acute care hospitals from the province of Québec. This study was set up to investigate the association between the psychosocial environment of work and mental health. After adjusting for confounding factors, a combination of high psychological demands and low decision latitude was associated with psychological distress and emotional exhaustion, one of the three dimensions of burnout. Social support at work, although associated with each of the mental health indicators, did not modify their association with job strain. The present study identified conditions of the work environment that are modifiable and provide the basis for interventions that focus beyond the modification of individual coping strategies.