Bupropion is a novel, structurally unique (single ring) compound, radically different from tricyclic antidepressants in its pharmacologic profile. In a random assignment, double-blind, long-term follow-up study of 60 depressed in- and outpatients (DSM-III criteria) in eight centers, the antidepressant actions of bupropion and amitriptyline were compared. Bupropion was as effective as amitriptyline in reducing depressive symptoms over a 6-month period, as measured by Hamilton depression and anxiety scales and Clinical Global Impression scores. Unlike amitriptyline, bupropion did not increase uric acid or cholesterol levels, and was not associated with weight gain. Bupropion was better tolerated than amitriptyline, the most commonly prescribed antidepressant.