The efficacy and safety of two dose schedules of the 5-HT3 antagonist ondansetron (Zofran) were studied in 35 patients (group A: 19 patients, group B: 16 patients) previously refractory to standard antiemetics after non-cisplatin-based chemotherapy (greater than 5 emetic episodes). The maintenance of the antiemetic efficacy of ondansetron was further studied in 28 patients (13 A, 15 B) in respectively 36 and 48 retreatment courses. Ondansetron was administered as an 8 mg loading dose (A: 4 mg i.v. + 4 mg orally; B: 8 mg i.v.), followed by oral treatment for 5 days (A: 6-hourly; B: 8 mg 8-hourly). In the first treatment cycle acute emesis was completely controlled in 53% of the patients in group A and in 50% of the patients in group B. Delayed emesis was absent in 75% and 38% of the patients in group A and B respectively. In a second treatment cycle acute antiemetic control was achieved in 54% and 53% of the patients in group A and B respectively. Over the third and fourth subsequent treatments, complete control occurred in 56% and 38% of the patients in group A, and in 46% and 56% of the patients in group B respectively. Delayed emesis did not occur over the following courses in 62%, 89% and 75% of the patients on regimen A, in 57%, 60% and 63% of the patients on regimen B. The observed adverse effects were headache (37%) and constipation (42%). No extrapyramidal reactions were seen. Ondansetron is able to re-establish an acceptable antiemetic control in previously refractory patients on non-cisplatin-based chemotherapy, without major toxicity. This efficacy is maintained over the three following retreatment courses.