Ten ferrets were used in a crossover study to determine the sedative effects of intramuscularly administered diazepam (3 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); acepromazine (0.1 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight); and xylazine (2 mg/kg body weight)-butorphanol (0.2 mg/kg body weight)-ketamine (15 mg/kg body weight). All of the ferrets became laterally recumbent following the administration of each drug combination. The xylazine-butorphanol-ketamine combination induced significantly longer (p less than 0.05) durations of tail-clamp analgesia (mean+/-standard deviation [SD], 81.0+/-19.1 min versus 20.5+/-25.4 min and 30.0+/-26.9 min), dorsal recumbency (mean+/-SD, 94.6+/-13.6 min versus 75. 6+/-34.7 min and 55.2+24.8 min), and muscle relaxation suitable for endotracheal intubation (mean+/-SD, 67.1+/-23.0 min versus 7.0+/-22.1 min and 9.5+/-15.4 min) than the diazepam-butorphanol-ketamine and acepromazine-butorphanol-ketamine combinations, respectively. The recovery time from dorsal recumbency to standing was not significantly different among the three treatment groups. The heart rate was significantly lower in the xylazine-butorphanol-ketamine group; however, systolic blood pressure was not significantly different among the treatment groups. Ventilatory function was more depressed in the diazepam-butorphanol-ketamine and xylazine-butorphanol-ketamine groups than in the acepromazine-butorphanol-ketamine group. A period (approximately 45 minutes) of hypoxia was observed in the xylazine-butorphanol-ketamine-treated ferret. Of the three combinations evaluated in ferrets, xylazine-butorphanol-ketamine was concluded to be the most effective anesthetic combination. However, hypoxemia and ventricular arrhythmias were observed in the xylazine-butorphanol-ketamine-treated ferrets, so the effectiveness of the xylazine-butorphanol-ketamine combination should be weighed against its cardiorespiratory side effects.