Rigorous criteria were used to select women with severe premenstrual syndrome for inclusion in an 8-month double-blind placebo-controlled clinical trial of progesterone vaginal suppositories. Following a control month without treatment, progesterone (200 mg in polyethylene glycol base) or placebo was self administered twice daily by vaginal suppository for a minimum of 12 days before the onset of menstruation for 3 months. Crossover to the opposite medication for a further 3 months was followed by a final control cycle without treatment in month 8. Physician contact was minimized throughout the study to avoid any possible positive effects of psychological support which may have confounded past investigations. Detailed self-report questionnaires were completed every 3 days for the duration of the study. Although the attrition rate was high, 20 women completed the trial and their records are analyzed here. The results of this trial indicate that the response to vaginal progesterone in these dosages is, at best, marginal and not significantly different from response with placebo use.