The results of a double-blind trial of a tetracyclic antidepressant, maprotiline (Ludiomil) and a conventional tricyclic, amitriptyline (Elavil), in 67 ambulatory depressives are reported. Hamilton's Rating Scale for Depression was the main outcome criterion. No statistically significant differences were found between the drugs in onset of action, efficacy, side effects or predictors of response. Patients on either drug showed a significant reduction in symptoms after 1 week of treatment and at the end of the trial. Both drugs were tolerated well. A review of double-blind comparisons of maprotiline and tricyclic antidepressants, spanning 13 countries, and including over 900 patients, both ambulatory and inpatient, shows essentially similar results. The main outcome criterion in all these studies was manifest psychopathology assessed on the Hamilton Rating Scale for Depression by the treating physician. The absence of additional types of outcome criteria or assessment techniques, which may have detected differences in motor activity or drive as originally postulated, may have obscured results which were expected to be subtle.