We tested a model in which perceived workload and autonomy were hypothesised to mediate the effects of work hours and caseload on physician burnout. The study was based on data provided by 890 specialists representing six medical specialties. We used structural equation modeling to test our hypotheses. Controlling for the effects of gender, seniority, and the specialists' academic affiliation, we found that the study data fit the hypothesised model-reflecting these hypotheses-quite well. As expected, workload predicted higher levels of global burnout and physical fatigue, while autonomy predicted lower levels of global burnout. Work hours and caseload predicted global burnout only indirectly, via their effects on either perceived workload or autonomy. These findings suggest that public policies, designed to reduce physician work hours in order to reduce burnout and improve patients' safety, should take into account physician perceived workload and autonomy. © 2009 The Authors. Applied Psychology: An International Review © 2009 International Association of Applied Psychology.