Predictive variables of response to imipramine and to phenelzine at 6 weeks and 6 months were studied in 116 patients suffering from major depression with melancholia (DSM-III). Several sociodemographic, clinical, and biological variables were studied. For imipramine-treated patients, high social support predicted a better response at 6 weeks, while development of hypomania during follow-up was associated with a better response at 6 weeks; absence of life events during the 6-month follow-up and initial non-suppression of dexamethasone predicted a better outcome at 6 months. For phenelzine-treated patients, development of hypomania during follow-up was associated with a better outcome at 6 months and absence of life events prior to the onset of the episode was associated with a worse outcome at 6 months.