Cyclophosphamide (177 mg/kg, IV: n = 8) produced a biphasic emetic response in the ferret with a mean +/- SE of 23.3 +/- 4.0 emetic episodes during a 4-h observation period. The emetic profile of cyclophosphamide showed a first phase with 18.6 +/- 3.9 episodes and a second phase with 4.7 +/- 1.2 episodes. Ondansetron (0.07 and 0.13 mg/kg, IV) and droperidol (0.25 and 0.79 mg/kg, IV) significantly reduced the number of emetic episodes in the first phase. Metoclopramide (2.24, 4.08, and 7.07 mg/kg, IV) also significantly reduced the number of emetic episodes in the first phase, and the dose of 7.07 mg/kg completely prevented emetic episodes in the second phase. In addition, ondansetron-treated ferrets (0.04, 0.07, and 0.13 mg/kg, IV) had a significant increase in the number of emetic episodes in the second phase.