Summary: This study was designed to evaluate the effects of alterations of β-receptor activity on intercoronary collateral blood flow after acute coronary artery occlusion in the awake dog. Blood flow following acute circumflex coronary occlusion was measured during: 1) control conditions; 2) selective β1-blockade with practolol; 3) combined β1 and β2 blockade with propranolol; and 4) selective β2 stimulation. Neither practolol nor propranolol significantly altered the volume or distribution of blood flow into the normally perfused or ischaemic myocardial areas, while β2 stimulation increased blood flow to the normally perfused myocardium from 1.13 ± 0.12 to 1.28 ± 0.10 cm3·min-1·g-1 (P <0.05). This increase in flow, which was directed preferentially to the subepicardium, was mediated by a significant decrease in coronary vascular resistance. In contrast to the effect on normally perfused myocardium, β2 stimulation resulted in a 47 ± 12% decrease in collateral flow into the central ischaemic zone (P <0.05), which was mediated by a combination of decreased arterial pressure and increased collateral vascular resistance during β2-agonist administration. Thus, although β2 stimulation produced a modest increase in blood flow to normally perfused myocardium, in the setting of acute myocardial ischaemia, β2 stimulation resulted in a significant decrease in intercoronary collateral flow.