The effect upon tryptophan metabolism of the use of combined oestrogen-progestagen oral contraceptives containing a low (0.05 mg) dose of oestrogen, or of the continuous administration of megestrol acetate, has been studied by determining the excretion of tryptophan metabolites in urine collected after a 2 g oral dose of the amino acid. An investigation of 10 women before being given oral contraceptives and after 21 days and three months of their use showed that xanthurenic acid excretion is increased within 21 days and that by three months the urinary levels of xanthurenic acid, kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid may all be elevated. Ten other women studied after taking a combined type of oral contraceptive for six months or longer excreted significantly higher levels of all four metabolites than did those who had been treated with these steroids for only three months. The abnormal urinary excretion of tryptophan metabolites was completely reversed by treatment with pyridoxine hydrochloride, 20 mg daily for one month. Studies of four women when they were taking an oestrogen-containing oral contraceptive and at intervals after they had discontinued its use showed that abnormal tryptophan metabolism may persist for three months or longer. Megestrol acetate, a progestagen used as an oral contraceptive, was found to have no significant effect upon tryptophan metabolism.The possible clinical significance of the effects of oral contraceptives upon tryptophan metabolism is discussed.