A double-blind clinical trial was undertaken to evaluate the clinical efficacy and safety of fluoxetine compared with imipramine in the treatment of 59 outpatients suffering from major depressive disorder. The mean scores of all depression rating scales showed that the drugs had comparable efficacy. The side effect profile of imipramine was found to be mainly anticholinergic, which was not the case for fluoxetine, where it was mainly found to be gastrointestinal, such as nausea and diarrhoea. In both groups the total number of adverse events reported were the same. Fluoxetine treatment resulted in weight loss, whereas imipramine treatment resulted in a slight but significant weight increase.