Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of the basal metabolic activity and chai;e in serum leptin levels should be carried out.