Background: Premenstrual syndrome (PMS) is defined as the disabling and cyclic occurrence of emotional and behavioral symptom complex during the latter half of the menstrual cycle. Although its etiology is unknown, it has been speculated that premenstrual syndrome is linked to a deficiency of central serotoninergic activity. Method: The study consisted of a double-blind, placebo controlled trial of fluoxetine at a dose of 20 mg/day or placebo for three menstrual cycles. The 440 women who appeared to meet the eligibility criteria were instructed to record the Calendar of Premenstrual Experiences (CPE) scale for two complete menstrual cycles. Of 410 women who successfully completed two cycles of recording their symptoms daily only 35 met the criteria for PMS. These criteria included psychiatric interviews which were made before treatment. Thirty-five PMS patients were randomized into placebo or fluoxetine treatment groups. Results: Our study suggests that fluoxetine at a dose of 20 mg per day was significantly superior to placebo in alleviating the symptoms of PMS. The most common side effects were gastrointestinal irritability (15%), insomnia (11%) and sexual dysfunction (8.5%). Conclusion: Fluoxetine is an effective and well-tolerated drug and appears to have considerable promise in treating a range of symptoms in women with PMS.