We tested the hypothesis that an insulin infusion would effectively treat bupivacaine-induced cardiac depression in dogs. In 24 mongrel dogs anesthetized with pentobarbital (5 mgkg(-1)h(-1), IV), 0.5% bupivacaine was administrated at a rate of 0.5 mgkg(-1)min(-1) until the mixed venous oxygen saturation decreased to 60% or less. The bupivacaine infusion induced a decrease in mean arterial pressure, cardiac output, and heart rate. The dogs were randomly assigned to one of four groups after the end of bupivacaine infusion. The Control (C, n = 6) and Glucose (G, n = 6) groups received an IV infusion of normal saline (2 mL/kg) and glucose (2 mL/kg of 50% dextrose in water) for 15 min, respectively. The Insulin-Glucose (IG, n = 6) group received an IV bolus of regular insulin (1 U/kg), plus a glucose infusion (2 mL/kg of 50% dextrose in water) for 15 min. The Insulin-Glucose-Potassium (IGK, n = 6) group received the same dose of insulin and glucose as the IG group, plus potassium (1-3 mEqkg(-1)h(-1)). Mean arterial pressure, cardiac output, heart rate, and mixed venous oxygen saturation recovered toward baseline level more rapidly in the IG and IGK groups than in the C group (within 5 min versus more than 20 min). These results suggest that the infusion of insulin and glucose might reverse bupivacaine-induced cardiac depression in dogs. CONCLUSIONS We found that insulin and glucose rapidly reversed hemodynamic abnormality in dogs with bupivacaine-induced cardiac depression. This study implies a possible clinical application of insulin treatment for bupivacaine-induced cardiac depression.