Résumé : A multicentre study compared the antidepressant efficacy and the tolerance of milnacipran (200 mg/d) and amitriptyline (150 mg/d) in two parallel groups of 43 major depressive inpatients, endogenous subtype, as defined by Research Diagnostic Criteria. The duration of the study was 4 weeks, with weekly assessments by means of the Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI) and a checklist of symptoms and side‐effects. Results showed similar improvement in both groups but better tolerance with milnacipran (less drowsiness and anticholinergic side‐effects), reflected in the better scores on the therapeutic index of the CGI. The clinical profile of the two drugs was somewhat different with more transitory sedation with amitriptyline and more improvement in concentration difficulties with milnacipran during the first weeks of the study associated with more effect on retardation with milnacipran at the end of the study. Copyright © 1989 John Wiley & Sons, Ltd.