Alprazolam appears to be an effective antidepressant in the treatment of outpatients who have a diagnosis of major depressive disorder. The authors have reviewed six controlled double-blind studies of alprazolam in the treatment of depression. Four of the six studies included only outpatients and clearly demonstrated a clinical effectiveness comparable to that of the tricyclics but with fewer, less severe side effects and better tolerance. The other two studies involved both inpatients and outpatients, so no conclusions can be drawn regarding the effectiveness of alprazolam in an inpatient population; further controlled studies are needed to answer this question. No satisfactory explanation exists for the mechanism of alprazolam's proposed antidepressant action.