The prostaglandin system is thought to play a role in the etiology of the premenstrual syndrome. Many authors describe that prostaglandins are involved in both central and peripheral symptoms. To test this hypothesis, we studied the effects of naproxen sodium treatment (550 mg twice daily, from day –7, in relation to next menses, to the 4th day of the cycle) in 34 patients suffering from premenstrual syndrome. Six cases dropped out. Fourteen women were given placebo for the first three cycles of the trial, followed by active drug. The other 14 patients were given naproxen sodium, beginning from the first cycle. In order to evaluate premenstrual symptoms, the Moos menstrual distress questionnaire was prospectively applied during the 2-month run-in period and at the 3rd and 6th cycles of treatment. During our double-blind naproxen sodium study, both menstrual and premenstrual ‘pain’ decreased during active drug treatment, while placebo was ineffective. We also obtained a significant improvement of premenstrual ‘behavioral changes’ which is probably related to the relief of painful symptomatology. In conclusion, this study indicates that naproxen sodium is a useful and safe drug in the treatment of premenstrual and menstrual pain related symptoms.