Sixty-two patients treated for the first time with i.v. CMF were included in a double-blind comparative study aimed at evaluating the efficacy of 3 different drugs (methylprednisolone (MP), metoclopramide (MTC), and domperidone (DMP) in preventing chemotherapy-induced nausea and vomiting. Complete protection from vomiting/nausea was obtained in 85%/80% in the group treated with MP; in 60%/65% in the group treated with MTC and in 38%/42% in the group treated with DMP. Average number of vomiting episodes was 2.4 with MP, and 1.7 with MTC and 6.2 with DMP. Older patients seem to be a prognostically unfavorable subgroup. Side-effects were mild and infrequent. We conclude that MP and MTC are probably equally efficacious antiemetic treatments in patients undergoing i.v. CMF chemotherapy, but due to the risk of extrapyramidal reactions with MTC, MP probably should be the treatment of choice in these patients.