Using an in vitro system to evaluate the simultaneous use of two drugs, we previously have confirmed the synergism of vincristine and prednisolone cytotoxicity against lymphoid cells. Experiments were now carried out to determine whether other steroid hormones can be substituted for prednisolone. Partial or complete potentiation of vincristine cytotoxicity comparable to that achieved by the addition of prednisolone was observed when the latter drug was replaced by a variety of mineralocorticoids (aldosterone, desoxycorticosterone and fludrocortisone), glucocorticoids (hydrocortisone, dexamethasone), androgens (testosterone, methyltestosterone, androsterone, dehydroepiandrosterone, etiocholanolone), estrogens (estrone, 17-beta estradiol) and progestins (progesterone, pregnanediol). No potentiation of cytotoxicity was observed when nonsteroidal hormones (thyroxin, ACTH) were added to vincristine. It is concluded that a wide variety of compounds with the basic perhydrocyclopentanophenanthrene nucleus of the steroid molecule are capable of enhancing the cytotoxicity achieved with vincristine.