Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature, but currently none of them is generally accepted. For the treatment of these conditions, only few recommendations based on empirical data are available. We conducted a randomized double-blind multicentre study in depressed outpatients comparing paroxetine and maprotiline in both patients with minor (n = 245) and major depression (n = 298). For the diagnosis, Research Diagnostic Criteria were used in a modified version. Two response criteria were applied: a reduction of 50% or more in total HAMD-17 scores from baseline (criterion 1), and a reduction of the HAMD-17 total score to 9 points or less (criterion 2). A completer and an endpoint analysis was performed. For patients with minor depression, remarkably high response rates were found for paroxetine (criterion 1: 90.9% completer, 82.1% endpoint; criterion 2: 89.1% completer, 82.4% endpoint) while the respective rates for maprotiline tended to be lower (criterion 1: 80.4% completer, 71.4% endpoint; criterion 2: 84.9% completer; 76.1% endpoint). Response rates in patients with major depression were for paroxetine: criterion 1: 74.3% completer, 62.8% endpoint; criterion 2: 76.4% completer, 65.2% endpoint; and for maprotiline: criterion 1:82.4% completer, 68.5% endpoint; criterion 2: 80.6% completer; 66.0% endpoint, which resembles rates reported from previous antidepressant trials. Both drugs were generally well tolerated. Though no placebo control was carried out, our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine, but also with maprotiline at a favourable risk/benefit ratio.