In order to understand the possible 5-hydroxytryptamine (5HT) anomalies in migraine, particularly in the period before the headache attack, we compared the levels of 5HT, its stable metabolite 5-hydroxyindoleacetic acid (5HIAA) and platelet monoaminoxidase (MAO) activity in patients with menstrual migraine with those of healthy female controls. In every subject, blood samples were drawn during both follicular and late luteal phases of the menstrual cycle. In controls, platelet 5HT levels remained stable, whereas 5HIAA levels and MAO activity were higher in the luteal than in the follicular phase, suggesting an increased catabolism of 5HT which occurs physiologically just before menses. In menstrual migraine 5HIAA levels and MAO activity showed similar changes with higher values in the luteal than in the follicular phase. The luteal phase values were significantly higher than those of controls. Also, and in contrast to controls, 5HT levels decreased in the luteal phase. These data suggest that 5HT availability is reduced in menstrual migraine, possibly due to an increased catabolism and/or to a reduced synthesis, and hence predisposes patients to migraine attacks.