The design and the main therapeutic results of 3 controlled double-blind studies comparing moclobemide with tricyclics and/or placebo in depressed patients are presented. Moclobemide, a reversible inhibitor of monoamine oxidase (RIMA), preferentially inhibits MAO-A. It showed good efficacy in major depression (DSM-III), both endogenous and non-endogenous. The 3 studies included a total of 763 patients. The therapeutic results are similar to those observed with tricyclics (2/3 good responders). Tolerability was significantly better. The onset of action was evaluated in 2 studies and was faster in the patients treated with moclobemide. The fact that reversible inhibitors of MAO-A demonstrate good efficacy independently of the diagnostic category of depression is an important new finding.