The effect of propranolol (0.1 mg/kg i.v.) on distal coronary pressure (DCP), distal bed (DR) and stenosis resistances (SR) and regional myocardial blood flow [endocardial-epicardial (endo/epi)] was studied in two groups of anesthetized dogs with a severe stenosis of the left circumflex coronary artery. In group 1, the ability of the DR to autoregulate was left intact, whereas in group 2, the DR was maximally dilated by pretreatment with the coronary vasodilator, chromonar. Despite similar global hemodynamic effects in both groups after propranolol treatment significant differences were observed in the ischemic area. In group 1, propranolol produced a significant increase in subendo blood flow, endo/epi and DCP in the ischemic region. In addition, DR (1.7 +/- 0.4 to 3.3 +/- 0.6 U) increased and SR decreased (3.4 +/- 0.5 to 1.7 +/- 0.3 U) significantly. In group 2, the changes in endo/epi, DCP, DR and SR were prevented by maximal vasodilation. These results suggest that the favorable changes produced by propranolol on ischemic myocardium are the result of a restoration of the ability of the resistance vessels to autoregulate. This allows for a passive decrease in coronary arteriolar dilation which results in an increase in DR and DCP and a decrease in SR. The increase in DCP may also contribute to the increase in ischemic subendo blood flow after propranolol.