The addition of high-dose methylprednisolone (120 mg given i.v. and repeated after a 4-h interval) to a conventional antiemetic regimen consisting of metoclopramide (0.5 mg/kg given as an i.v. bolus over 30 min followed by 1 mg/kg given as a continuous infusion over 24 h) and alprazolam (0.5 mg given p.o.) was evaluated in a randomized study of leukemic patients undergoing anthracycline-containing multiple-day chemotherapy. Double-blind analysis was done in 30 patients who completed a total of 40 treatment courses. Cumulative 3-day results revealed complete control of nausea in 66% of patients and complete control of emesis in 77% of cases. The addition of methylprednisolone significantly reduced the occurrence of nausea (p = 0.003) and emesis (P = 0.06). Moreover, antiemetic rescue with chlorpromazine was less frequently necessary in patients receiving corticosteroids (P = 0.02). No harmful side effect was observed, and the incidence of severe infectious episodes was similar in both arms. We conclude that high-dose methylprednisolone can improve the efficacy of metoclopramide and alprazolam in controlling nausea and emesis induced by anthracycline-containing multiple-day chemotherapy in patients with acute myeloblastic leukemia.