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BACKGROUND: The prophylactic use of 5-HT(3) receptor antagonists (setrons), after the first 24 h (acute phase) of exposure to emetic chemotherapy, to decrease the incidence of 'delayed phase' emesis increases costs. We designed a study to evaluate the efficacy of a setron (granisetron) in the delayed phase, compared with metoclopramide, each combined with a corticosteroid. PATIENTS AND METHODS: Patients on their first course of single-day emetic chemotherapy (cisplatin, carboplatin, doxorubicin, cyclophosphamide and others) received granisetron 2 mg p.o. and dexamethasone 8 mg p.o. on day 1, followed for 5 days by dexamethasone 4 mg p.o. od combined with either metoclopramide 20 mg p.o. tds or granisetron 1 mg bd in a double-blinded double-dummy protocol. Patients evaluated the results using a diary card. Randomization was stratified by institution, sex, emetic chemotherapy naïve versus previous, alcohol consumption and platinum versus non-platinum regimen. RESULTS: 131 evaluable patients received granisetron in the delayed phase, and 127 received metoclopramide. Control of acute emesis in both arms was similar (86% granisetron; 85% metoclopramide). The 35 patients experiencing acute emesis had poor control in the delayed phase, with only four granisetron and three metoclopramide patients having no or mild nausea and no vomiting. CONCLUSIONS: In daily practice, a combination of oral dexamethasone and oral granisetron achieves an extremely high control of acute emesis (86% protection). Our data suggest that routine prescription of setrons for delayed phase control is not advisable as it increases costs without any benefit for the majority of patients. Delayed emesis in the rare patients with acute phase emesis remains an unsolved problem.