Thirty patients with well-defined symptoms of pre-menstrual syndrome were randomly treated with the antibiotic doxycycline or placebo. The antibiotic-treated group showed a highly significant reduction of symptoms. Subsequent antibiotic treatment of the original placebo group similarly diminished the symptoms in this group. A 6-month follow-up demonstrated that the improvement in symptom scores was permanent and independent from the presence of the antibiotic. Luteal phase endometrial biopsies showed a high incidence of out-of-phase endometrium. An unexpectedly high percentage of endometrial biopsy cultures yielded positive findings for mycoplasma, Chlamydia trachomatis and anaerobic bacteria. There were no characteristic hormonal changes in this study group. An infectious aetiology, possibly a sub-clinical endometrial or ovarian infection, behind certain cases of pre-menstrual syndrome is postulated.