The purpose of this study was to examine the feasibility of a combination chemotherapy protocol ("CYCLONE") in cats, utilizing mitoxantrone and cyclophosphamide. Three normal adult cats were administered mitoxantrone (6.5 mg/m2 intravenously) and cyclophosphamide (100 mg/m2 intravenously) every 21 days for a total of three doses. Individual white blood cell count nadirs (range, 2.0-9.5 x 10(9)/L) and neutrophil count nadirs (range, 0.3 to 5.0 x 10(9)/L) occurred between days 2 and 10 after each dose of chemotherapy. Mean white blood cell count nadirs (range of mean, 5.5 to 8.4 x 10(9)/L) occurred between days 6 and 8, as did the mean neutrophil count nadir (range of mean, 1.7-4.0 x 10(9)/L). Side effects were limited to transient appetite suppression in one cat and loose stools in two cats. Myelosuppression and gastrointestinal side effects were comparable to those observed with single-agent mitoxantrone protocols. Further investigation of this protocol is warranted.