The purpose of this study was to determine the effect of acute and chronic propranolol on heart size and regional O2 supply/consumption variables in thyroxine (T4)-treated rabbit hearts. New Zealand white rabbits were given 0.5 mg/kg T4 for 3 or 16 days with and without concomitant 2 mg/kg propranolol. Another group was given 16 days of propranolol alone and another 3-day T4 group was given 2 mg/kg propranolol 1 h before the experiment began. Another group served as control. Myocardial blood flows were determined using radioactive microspheres and small arteriolar and venous O2 saturations were determined using microspectrophotometry. Treatment with T4 for 3 or 16 days increased the heart weight/body weight ratio, myocardial blood flow, and regional O2 consumption. 16-day T4 treatment resulted in myocardial flow 195% and O2 consumption 300% above control group values. When propranolol was given chronically along with T4, heart weight/body weight ratios did not increase to the degree seen with 3 or 16 days of T4, alone. Propranolol given acutely in 3-day T4-treated animals, resulted in a reduced O2 consumption and O2 extraction, though not to the extent seen with chronic propranolol treatment of T4-treated animals. Acute propranolol treatment slightly reduced myocardial blood flow in 3-day T4-treated animals, while chronic treatment significantly reduced it. Chronic propranolol treatment in 16-day T4-treated animals resulted in a significant reduction in flow and O2 consumption. Thus, T4 treatment increased O2 consumption, flow, and heart size and these effects could be attenuated using acute and chronic propranolol.