Carbohydrate metabolism and vitamin-B6 status were assessed before and after pyridoxine administration in 46 women taking combined oestrogen-progestagen oral contraceptives (O.C.). 18 women had evidence of tissue depletion of vitamin B6, although all the women had abnormal tryptophan metabolism, including increased urinary xanthurenic acid (X.A.) excretion. In the women with vitamin B6 deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction in plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes in carbohydrate metabolism were not found in the 28 non-vitamin-B6-deficient women. These results indicate that carbohydrate intolerance in women on O.C. is unlikely to be mediated by the formation of a complex of X.A. with insulin, as has formerly been proposed. Since the synthesis of the tryptophan metabolite quinolinic acid, an inhibitor of the heptaic enzyme phosphoenolpyruvate carboxykinase, may be enhanced by the administration of pyridoxine, it is suggested that this metabolite might be the important factor in the improvement of glucose tolerance in the vitamin-B6-deficient women. This conclusion is supported by the improvement in glucose tolerance observed in 6 women on O.C. and in 4 patients with glucocorticoid excess who were not vitamin-B6 deficient, when they were given tryptophan to augment the synthesis of quinolinic acid.