Whole-blood serotonin levels in 14 subjects with well documented premenstrual syndrome and 13 age-matched controls were compared. Serotonin levels of premenstrual syndrome subjects were significantly lower during the last ten days of the menstrual cycle. No significant differences were noted in levels of serum estradiol and progesterone. Decreased serotonin is known to be associated with depression in humans, and nonhuman primates have exhibited abnormal behavioral profiles when given serotonin antagonists. The present observation suggests that the physiologic basis of premenstrual syndrome involves an alteration in serotonin metabolism.