Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double-blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction.