OBJECTIVE-To compare the effect of oral administration of tramadol alone and with IV administration of butorphanol or hydromorphone on the minimum alveolar concentration (MAC) of sevoflurane in cats. DESIGN-Crossover study. ANIMALS-8 Healthy 3-year-old cats. PROCEDURES-Cats were anesthetized with sevoflurane in 100% oxygen. A standard tail clamp method was used to determine the MAC of sevoflurane following administration of tramadol (8.6 to 11.6 mg/kg [3.6 to 5.3 mg/lb], PO, 5 minutes before induction of anesthesia), butorphanol (0.4 mg/kg [0.18 mg/lb], IV, 30 minutes after induction), hydromorphone (0.1 mg/kg [0.04 mg/lb], IV, 30 minutes after induction), saline (0.9% NaCl) solution (0.05 mL/kg [0.023 mL/lb], IV, 30 minutes after induction), or tramadol with butorphanol or with hydromorphone (same doses and routes of administration). Naloxone (0.02 mg/kg [0.009 mg/lb], IV) was used to reverse the effects of treatments, and MACs were redetermined. RESULTS-Mean +/- SEM MACs for sevoflurane after administration of tramadol (1.48 +/- 0.20%), butorphanol (1.20 +/- 0.16%), hydromorphone (1.76 +/- 0.15%), tramadol and butorphanol (1.48 +/- 0.20%), and tramadol and hydromorphone (1.85 +/- 0.20%) were significantly less than those after administration of saline solution (2.45 +/- 0.22%). Naloxone reversed the reductions in MACs. CONCLUSIONS AND CLINICAL RELEVANCE-Administration of tramadol, butorphanol, or hydromorphone reduced the MAC of sevoflurane in cats, compared with that in cats treated with saline solution. The reductions detected were likely mediated by effects of the drugs on opioid receptors. An additional reduction in MAC was not detected when tramadol was administered with butorphanol or hydromorphone.