Seventy-eight patients with advanced breast cancer were given fluorouracil by a slow infusion induction course starting in the immediate postoperative period after adrenalectomy, followed by direct weekly maintenance injections. By this method, fluorouracil was effective and well tolerated, with no greater toxicity than that from drug similarly administered in combination with prednisone to 27 nonadrenalectomized patients and to 21 patients given drug alone. There were no drug deaths in adrenalectomized patients; the incidence of adrenal insufficiency was not increased; and a greater corticoid replacement requirement was not seen. Greater hematologic and gastrointestinal toxicity as well as two toxic deaths were seen in patients given prednisone and fluorouracil. Drug dose, frequency of bony and liver metastases, concomitant irradiation, and previous myelosuppressive therapy did not contribute to this difference; older patients and advanced visceral disease appeared to be the major influencing factors.