PIP: The biological mechanisms through which oral contraceptives influence the central nervous system and produce depression were examined. Oral contraceptives reduce the level of serotonin and norepinephrine available at the central adrenergic receptor sites, alter folate and B12 levels, and perhaps influence hypothalamic releasing hormone levels. The level of serotonin is influenced in the following manner. The estrogens in oral contraceptives increase tryptophan available for the brain to convert to serotonin and tryptamine. Depression is associated with lower levels of serotonin, tryptamine, and perhaps tryptophan in the brain. Estrogens in oral contraceptives may also alter pryridoxal phosphate which in turn affects the production of serotonin. Oral contraceptives possibly lower norepinephrine levels by 1) decreasing tyrosine; 2) influencing coenzymes necessary to norepinephrine production; and 3) increasing monoamine oxidase levels. Oral contraceptives apparently inhibit the metabolism of folate and B12, and lower levels of these substances are associated with depressive symptoms. Decreased norepinephrine and serotonin levels may inhibit the release of gonadotrophin-releasing hormones, and these hormones may in turn influence behavior. Recommendations to clinicians were: 1) patients should be screened for a history of depression prior to prescribing oral contraceptives; 2) pill users should be monitored for depression; and 3) 25 mg daily of pyxidoxine should be administered if a patient taking oral contraceptives is deficient in B6.