We evaluated the influence of time of recanalization or degree of initial leptomeningeal collateral blood flow in cardioembolic or arterio-arterial middle cerebral artery (MCA) occlusion on infarct size and clinical outcome in a series of 34 consecutive acute stroke patients with main stem (N = 31) or major branch (N = 3) occlusions using CT, initial cerebral arteriography (N = 21), repetitive close-meshed transcranial Doppler ultrasonography, and a neurologic stroke scale. We treated 15 patients with tissue plasminogen activator intravenously within the first 6 hours. The type and size of infarction depended on the location of the occluding lesions within the MCA trunk. Proximal MCA occlusion always led to infarction involving the striatum and internal capsule. Sixty-five percent of patients showed recanalization of the occluded MCA within 1 week. Following MCA recanalization, hyperperfusion was present in 38 to 44% of cases. There was a marginally significant relation between size of infarction on CT and recanalization time within the first 24 hours. The more rapidly recanalization occurred, the smaller the size of the infarct. When recanalization time was greater than 8 hours, the lesions always extended to the cortex. An additional good leptomeningeal collateral blood flow significantly reduced the size of the infarct and improved clinical outcome after 17 days and after 10 months. Early recanalization of embolic MCA occlusions within up to 8 hours, in conjunction with good transcortical collateralization, has a favorable impact on infarct size and outcome and may constitute the therapeutic window of opportunity.