Nausea and vomiting remain common and debilitating side effects of therapy with many anticancer drugs. Recent reports have shown that both metoclopramide and dexamethasone are effective drugs for the treatment of severe nausea and vomiting caused by cis-platinum. A double-blind crossover study comparing the antiemetic properties of high-dose oral and intravenous regimens of metoclopramide and dexamethasone in outpatients was carried out. Standardized patient questionnaires and interviews were used to evaluate response. Dexamethasone and metoclopramide protected against more than five episodes of emesis in 48% and 40% of patients, respectively. Nausea persisted for less than six hours in 45% of patients on dexamethasone and in 37% on metoclopramide. The antiemetic efficacy of both regimens was retained through repeated courses of chemotherapy. Side effects were minimal with dexamethasone; however, 33% of patients experienced unacceptable extrapyramidal side effects to metoclopramide. Patient preference was significantly in favor of dexamethasone: 70% of patients chose to continue dexamethasone compared to 22% who preferred metoclopramide and 8% who chose other antiemetics. Dexamethasone was the preferred antiemetic in this patient population due to minimal side effects.