Acute occlusion of the circumflex branch of the left coronary artery was produced in chronically instrumented conscious dogs. Tracer microspheres were used to measure during an established time period, the distribution of collateral flow within the infarcting myocardium. For up to 2 hours after coronary occlusion the amount and distribution of the collateral flow remained unchanged. Two to 4 hours after coronary occlusion the subendocardial flow fell to almost zero and the subepicardial flow rose. Between 6 and 48 hours subepicardial and total collateral flow rose markedly. A no-reflow phenomenon is responsible for the decline of collateral flow in the subendocardium. Evidence for this hypothesis was provided by releasing the artery 1,2, 4 and 6 hours after occlusion. The amount of subendocardium that could not be reperfused was small after 1 hour and large after 6 hours of occlusion. When the total collateral flow was very low, the subepicardium was not able to be reperfused and a transmural myocardial infarction developed. We conclude that the time delay between onset of ischemia and the appearance of a no-reflow phenomenon depends upon the amount of collateral flow. The occurrence of a no-reflow phenomenon in the subendocardium increases the amount of flow to the subepicardium which increases its chances of survival. Beyond the sixth hour after occlusion the total amount of collateral flow increases which is interpreted as a reduction of collateral resistance by passive caliber changes of the collateral vessels. DNA-synthesis that signal active caliber changes through cellular proliferation were always detected 24 hours after complete occlusion of a coronary artery regardless whether the time between onset of stenosis until complete occlusion was varied between 36 hours and 5 days. When the time to complete occlusion was 4 days, myocardial infarction was prevented due to growth-transformation of pre-existing collaterals. Four phases of collateral reactions in acute coronary occlusion were observed: redistribution of available collateral flow in favor of the subepicardium (t = 1 to 4 hours after occlusion), 2) increase of total collateral flow due to passive "stretch" of collateral vessels (t = 4 to 24 hours after occlusion), 3) radial growth of collateral vessels due to active cellular proliferation, (t = 24 hours to 5 days) 4) cellular proliferation to ensure a normal wall thickness in growth'transformed collaterals (t = 5 days to 20 days after coronary occlusion). In subacute coronary occlusion the first phase does, of course, not apply.