Objective To determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats. Study design Prospective, randomized, crossover study. Animals Eight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 +/- 0.6 kg). Methods Each cat was instrumented with a wireless thermistor in the abdominal cavity. Temperature in all phases was recorded every 5 minutes for 5 hours. Population body temperature (PBT) was recorded for similar to 8 days. Baseline body temperature is the final 24 hours of the PBT. All injectable drugs were given intramuscularly. The cats were administered drugs in four phases: 1) hydromorphone (H) 0.05, 0.1, or 0.2 mg kg-1; 2) morphine (M) (0.5 mg kg-1), buprenorphine (BUP) (0.02 mg kg-1), or butorphanol (BUT) (0.2 mg kg-1); 3) ketamine (K) (5 mg kg-1) or ketamine (5 mg kg-1) plus hydromorphone (0.1 mg kg-1) (KH); 4) isoflurane in oxygen for 1 hour. Fifteen minutes prior to inhalant anesthetic, cats received either no premed (I), hydromorphone (0.1 mg kg-1) (IH), or hydromorphone (0.1 mg kg-1) plus ketamine (5 mg kg-1) (IHK). Results Mean PBT for all unmedicated cats was 38.9 +/- 0.6 degrees C (102.0 +/- 1 degrees F). The temperature of cats administered all doses of hydromorphone increased from baseline (p < 0.03) All four opioids (H, M, BUP and BUT) studied increased body temperature compared with baseline (p < 0.005). A significant difference was observed between baseline temperature values and those in treatment KH (p < 0.03). Following recovery from anesthesia, temperature in treatments IH and IHK was different from baseline (p < 0.002). Conclusions and clinical relevance All of the opioids tested, alone or in combination with ketamine or isoflurane, caused an increase in body temperature. The increase seen was mild to moderate (< 40.1 degrees C (104.2 degrees F) and self limiting.