It has been shown that a paradoxical pressor response to a β-blocker occurs in rats given an α-blocker. The dual-isotope microsphere technique was used to investigate the hemodynamic changes that accompany the pressor response to propranolol in phentolamine-treated, urethane-anesthetized rats. Rats were divided into four groups (n = 8 per group): group I received 10 min of saline infusion; group II received intravenous infusion of phentolamine (300 μg/kg/min) for 10 min; group III received intravenous injection of propranolol (100 μg/kg) after 20 min of phentolamine infusion, and group IV received intravenous injection of saline after 20 min of phentolamine infusion. In groups I and IV, saline did not cause any significant hemodynamic changes. In group II, phentolamine decreased the mean arterial pressure (MAP) and total peripheral resistance (TPR) by 34 ± 3 mm Hg and 0.28 ± 0.07 mm Hg/min/ml, respectively. Arterial conductances in the skeletal muscle and skin were increased to 157 and 165% of control values, respectively. Cardiac output and conductances in other tissues and organs were not significantly affected. In rats given phentolamine (group III), propranolol raised MAP (+40 ± 2 mm Hg) by increasing TPR (+0.41 ± 0.03 mm Hg/min/ml). Vascular conductances in the skeletal muscle, skin and kidneys were decreased to 38, 57 and 69% of control values, respectively. Conductances in other tissues and organs were not significantly affected. Our results show that propranolol raised MAP by increasing flow resistance, primarily via the reversal of the vasodilator effects of phentolamine in the muscle and skin.