Emotional upsets related to changes in ovarian hormones are highly prevalent and are responsible for psychiatric morbidity and mortality. Significant increases in acute psychiatric hospitalizations, suicidal activity, and other psychopathology occur during the premenstruum and during menstruation. This paper reviews evidence indicating that menstrual cycle psychopathology may be mediated by the effects of estrogen, progesterone, and possibly the renin—angiotensin—aldosterone system on the brain monoamines, norepinephrine, dopamine, and serotonin. During the menstrual cycle, psychopathology often begins with the onset of luteal estrogen—progesterone—angiotensin—aldosterone secretion and intensifies as these hormone levels later fall, prior to and during menstruation. Aldosterone is reported elevated in cases of premenstrual tension syndrome. There are numerous reports of affective upsets occurring with the use of estrogen—progestin oral contraceptives and following their withdrawal. Contraceptives stimulate the renin—angiotensin—aldosterone system and are reported useful in alleviating premenstrual—menstrual emotional upsets and postpartum depressive episodes. Affective lability, prevalent at parturition, occurs when estrogen, progesterone, and aldosterone levels are first high and later falling. Exogenous estrogen and progesterone profoundly affect mating activity in castrated rhesus monkeys, and cyclic fluctuations in sexual activity in humans may occur during the menstrual cycle. Much information links manic and depressive reactions with alterations in brain monoamines. Lithium, monoamine oxidase inhibitors, and tricylic antidepressants, specifically used to treat affective disorders, are reported useful in treating ovarian hormone—linked upsets. Similarities exist between changes in animal behavior caused by drugs altering affective states and the effects of ovarian hormones. Like certain antidepressants, estrogen induces hyperactivity in rats. Like reserpine, progesterone exhibits sedative and soporific effects. Sexual behavior in female rats is reported linked to changes in brain monoamines. Agents increasing brain monoamine levels and availability decrease mating responses, and monoamine depletors, such as reserpine may be substituted for progesterone in activating mating behavior. Serotonin and dopamine appear to be important in the regulation of ovulation. Brain norepinephrine varies with the phases of the rat estrus cycle. Castration increases brain norepinephrine and decreases brain dopamine. Exogenous estrogen decreases rat brain norepinephrine content. The monoamine-destroying enzymes, monoamine oxidase, and catechol O-methyl transferase are affected by ovarian steroids and show fluctuating levels during the reproductive cycle. The effects of reserpine, monoamine oxidase inhibitors, tricyclic antidepressants, and lithium on monoamines in neurophysiological preparations have been used as evidence supporting theories linking monoamine changes with human affective disorders. Estrogen, progesterone, and angiotensin also exhibit effects on in vitromonoamine systems. Like the tricyclic antidepressants, uptake of norepinephrine and dopamine by nerve endings is inhibited in the presence of estrogen, progesterone, and angiotensin. As with reserpine, the flow of these monoamines from nerve endings is increased by progesterone. Estrogen slows the flow of norepinephrine from nerve endings and decreases the electrically induced release of serotonin and norepinephrine from brain slices. The above information provides clues that ovarian hormone—linked psychopathology, like affective disorders in general, may be related to alterations in brain monoamines.