The metabolism of methionine was studied in 10 control and in 14 women using estrogen-containing oral contraceptives during 28 days of vitamin B6 deficiency and then for another 28 days while ingesting the same diet with daily supplements of 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride. Urinary cystathionine excretion after a 3-g load of L-methionine increased promptly in both groups and continued to increase throughout the 28 days of vitamin B6 depletion; there was no significant difference in the amount excreted by controls and oral contraceptive users. Two milligrams of pyridoxine-HCl restored the cystathionine excretion to predepletion levels within three to four weeks for both control and oral contraceptive users. Daily supplements of 0.8 mg of pyridoxine-HCl for as long as four weeks failed to restore cystathionine excretion to normal levels for either controls or contraceptive users; supplements of 2.0 mg met the vitamin B6 requirements for both groups. Urinary methionine, cysteine sulfinic acid, and taurine excretion did not differ significantly between the two groups at any time. The data indicate that oral contraceptive users are not generally different from non-users with respect to vitamin B6 requirements as evidenced by methionine metabolism.