In a previous study of propranolol poisoning, glucagon and milrinone significantly increased cardiac output, but the improvement caused by glucagon was almost entirely due to the chronotropic effect. This study investigates the combined effect of glucagon, in a dose not inducing tachycardia, and milrinone on beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV over ten minutes, dogs (N = 20) were divided into four treatment groups, group S (saline), group G (glucagon 2.5 micrograms/kg), group M (milrinone 100 micrograms/kg), and group G + M (glucagon 2.5 micrograms/kg plus milrinone 100 micrograms/kg). Hemodynamic parameters were observed over the next thirty minutes. Heart rate, cardiac output, and mean arterial pressure were decreased in all groups after the administration of propranolol. Heart rate, mean arterial pressure, cardiac output, and stroke volume recovered to the baseline values in group G + M. However, heart rate in group G + M showed a significant increase versus the other three groups. In a canine model of severe propranolol poisoning, the combined effect of glucagon 2.5 micrograms/kg and milrinone 100 micrograms/kg brought about a significant hemodynamic improvement, but it was accompanied by an excessive increase of heart rate. Combined therapy of milrinone and glucagon may not be preferable therapy in beta-blocker poisoning in the canine model.