A single i.p. injection of vincristine (1000 microgram/kg) into rats increased the plasma concentration of corticosterone after a latent period of 4 hr; the effect lasted for 48 hr. The response was dose related with the threshold dose being 100 microgram/kg and the maximal effect occurring after 250 microgram/kg. Vincristine also increased plasma corticosterone levels in hypophysectomized rats, suggesting that the drug may have a direct action on the adrenal gland. The injection of 500 or 1000 microgram/kg also reduced the plasma concentration of thyroid-stimulating hormone. Twelve and 18 hr after the injection of vincristine (1000 microgram/kg), the plasma concentration of thyroid-stimulating hormone was reduced, whereas the hypothalamic content of norepinephrine, a neurotransmitter involved in the regulation of thyrotropin-releasing hormone-thyroid-stimulating hormone secretion, remained unchanged. The adrenocortical stimulation produced by vincristine may play some role in the antineoplastic effects of this drug.