The effectiveness and good acceptability of tianeptine have been demonstrated in episodes of major depression without melancholia or signs of psychosis which are the valided indications of the tianeptine. In a way of research program, a multicenter study was conducted in 30 patients with D.S.M. III criteria for major depression with melancholia and signs of endogenicity as defined by the Newcastle scale. The patients were treated in a double-blind trial for 42 days. Administration of a placebo for 4 days prior to beginning the study was designed to eliminate rapid responders to placebo. The antidepressant effectiveness was evaluated on the Hamilton (HDRS), Montgomery and Asberg (MADRS) and global clinical impression (GCI) scales. The effect was satisfactory and statistically significant. Seventeen of the 30 patients (57 percent) included in this study improved with tianeptine (CGI-item 2). Results were comparable whatever the diagnosis established on DSM III criteria: bipolar depression, major depression, recurrent or isolated forms. The acceptability evaluated from patient complaints, measurement of blood pressure and laboratory tests was very satisfactory. Treatment was withdrawn in 14 patients with no subsequent withdrawal symptoms. These findings show that tianeptine can be prescribed with success for major depression episodes with melancholia (DSM III) and signs of endogenicity, although it cannot be concluded that patients should be given this treatment in first intention for this type of depression.