Serotonin reuptake inhibitors, such as dexfenfluramine, fluoxetine and fluvoxamine, have been proposed as therapeutical tools for the treatment of eating disorders and obesity. Sertraline, a SSRI used in the treatment of depression, interferes with eating behavior in animal models, but it has not been tested in obese humans. Aim of this study is the assessment of the effects of sertraline on eating attitudes and body weight in obese patients with and without mood disorders. A consecutive series of 65 obese out-patients aged 18-65 years, with a body mass index (BMI) > 30 kg/m2, was treated for 6 months with sertraline 150 mg/day per os, in addition to a cognitive-behavioral treatment (CBT). A consecutive series of 60 obese patients with similar characteristics, who were treated with CBT only, were used as control group. A greater reduction of BMI (mean +/- SD) was observed in sertraline-treated patients when compared to controls (from 35.3 +/- 5.7 to 32.0 +/- 5.4 kg/m2 in sertraline-treated patients, from 37.1 +/- 7.0 to 36.0 +/- 7.1 kg/m2 in controls; 6.5 +/- 5.4% vs. 3.0 +/- 6.3%; p < 0.01), while a similar change in eating attitudes (evaluated through the BITE questionnaire) was observed in both groups. Effects of sertraline on eating attitude and body weight were similar in patients with and without mood disorders. In conclusion, sertraline, administered together with CBT, seems to be more effective in inducing weight loss in obese patients when compared with CBT alone, and therefore it could be a useful tool in the first months of CBT for severe obesity.