Standard-dose (2 mg/day) oral granisetron seems to have more antiemetic efficacy than that of high-dose (0.5-1 mg/kg/dose) metoclopramide in moderately emetogenic chemotherapy. However, the cost of oral granisetron is much higher than that of metoclopramide so the authors tried to overcome this disadvantage by dose reduction and adding dexamethasone to enhance the antiemetic effect of oral granisetron. Twenty four young patients (aged < 50 years), with non-Hodgkin's lymphoma receiving CHOP-therapy were enrolled and evaluated in a randomized, double-blind, crossover study comparing the antiemetic efficacy, toxicity and patients' preference of a combination of low-dose oral granisetron plus intravenous dexamethasone (gran/dex) with a combination of high-dose metoclopramide plus intravenous dexamethasone (met/dex) on days 1-5 after chemotherapy. The acute, delayed (day 2-5) and 5-day total control of nausea and vomiting in the gran/dex group were significantly higher than those of the met/dex group (75.0% vs 25.0%; p-value = 0.004, 79.2% vs 33.3%; p-value = 0.007 and 75.0% vs 25.0%; p-value = 0.004, respectively). Except for extrapyramidal reactions in the met/dex group, the side effects in both groups were comparable. The mean total score of antiemetic preference in the gran/dex group was also significantly higher than that of the met/dex group (9.0 vs 7.5; p-value = 0.004). In conclusion, low-dose oral granisetron combined with intravenous dexamethasone had significantly higher protective effects against both acute and delayed nausea and vomiting induced by CHOP-therapy. Thus, this regimen may be considered as an alternative outpatient antiemetic treatment for young patients with non-Hodgkin's lymphoma.