Antidepressants are used commonly for the treatment of fibromyalgia syndrome (FMS). We investigated the efficacy and tolerability of moclobemide in this syndrome. Twenty one women with FMS who have severe depression according to Beck Depression Scale were included study. The average age was 45.6±12.1 years. The mean duration of symptoms was 8.3±5.6 years. Moclobemide was administered 300 mg p.o. twice daily for 45 days. The patients were evaluated at day 15 and 45. Before treatment, the score for pain was 7.6±1.3 according to VAS and pain decreased 24.6% at day 15 days and 48.1% at day 45 days. Before treatment, number of tender points was 12; it significantly decreased 23% on the 15th day and 46.7% after treatment. Before treatment, the score of pain related to the pressure of tender point (according to VAS) was 8.2±1.9; it significantly decreased 19.0% on the 15th day and 41.6% after treatment. Improvement in sleep disturbance was not significant (p>0.05). Before treatment, the duration of morning stiffness was 27.0±30.3 minutes; it was detected to be decreased as 35.7% and 64.2% at day 15 and 45, respectively. There was not a significant improvement in other symptoms. Good or very good improvement of 20% and 55% was detected at day 15 and 45. Side effects were 28.5% and 19% at control measures. Nausea and insomnia were the most common side effects. In all patients tolerability was assessed as good or very good at days 15 and 45. It is concluded that moclobemide 300 mg p.o. twice daily is effective and tolerable in patients with FMS who have severe depression.