OBJECTIVE To determine cardiorespiratory effects of a tiletamine/zolazepam-ketamine-detomidine (TZKD) combination in horses. METHODS 8 healthy adult horses. METHODS Horses were instrumented for measurement of cardiorespiratory, acid-base, and electrolyte values. Each horse was given xylazine (0.44 mg/kg of body weight, IV) 10 to 15 minutes prior to induction of recumbency by administration of the TZKD combination. Cardiorespiratory, acid-base, and electrolyte values were measured at 5-minute intervals for > or =30 minutes. RESULTS All horses became recumbent within 1 minute after IV administration of TZKD. Mean +/- SD duration of recumbency was 40+/-8 minutes. All horses regained standing position after < or =2 attempts. Quality of anesthesia and analgesia was determined to be satisfactory in all horses. Xylazine induced decreases in respiratory rate, heart rate, cardiac output, maximum rate of increase of right ventricular pressure, and rate pressure product. The PaCO2, right atrial pressure, and peripheral vascular resistance increased, whereas blood temperature, PO2, pHa, HCO3-, PCV, total solids, Na, and K values remained unchanged. Subsequent administration of TZKD caused right atrial pressure and PaCO2 to increase and PaO2 to decrease, compared with values obtained after xylazine administration. Remaining cardiorespiratory, acid-base, hematologic, and electrolyte values did not differ from those obtained after xylazine administration. CONCLUSIONS IV administration of TZKD induces short-term anesthesia in horses. Potential advantages of this drug combination are the small volume of drug administered; minimal cardiorespiratory depression; quality of induction and maintenance of, and recovery from, anesthesia; and duration of drug effects.