The plasma concentrations of branched-chain and aromatic amino acids, free tryptophan, and kynurenine have been determined in oral contraceptive users and comparable controls. There were no differences between progestogen users and controls in either of the biochemical measurements. The estrogen-progestogen users showed elevated plasma levels of total tryptophan and decreased levels of tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. There was a clear trend that the incidence of adverse reactions was related to the decrease in tyrosine levels. The plasma ratio of tryptophan to competing amino acids was increased in the estrogen-progestogen users, whereas the ratio of tyrosine to competitors was severely decreased suggesting a decreased brain tyrosine concentration. It is suggested that a substrate-limited reduction in brain noradrenaline synthesis may contribute to the occurrence of depressive symptoms in susceptible individuals on estrogen-progestogen contraceptives.