Abstract The development of fibrinolytic agents such as streptokinase and recombinant tissue type plasminogen activator (r-TPA) and other modalities of treatment in acute ischemic stroke, has raised the need for a more precise knowledge of the pathophysiology of the acute phases of ischemic stroke as it pertains to prediction of clinical outcome. In a prospective analysis, 80 patients were studied within less than 6 h from the onset of symptoms by means of a detailed protocol including clinical evaluation, cerebral computed tomography, digital angiography and ultrasound transcranial Doppler sonography. Early angiography revealed a complete arterial occlusion in 76% of cases, the majority of which were intracranial (66%). Seventy percent of the occlusions that were retested were removed within 1 week. Potential embolic sources were found in more than 80% of cases. Patients with documented intracranial occlusion and scarce or absent collateral filling at early angiography, had the worst clinical outcome ( P < 0.05), based on mortality data and the Canadian Neurological Scale. The 30-day mortality rate was 25%. Survival was significantly better ( P < 0.01) in patients with a Canadian Neurological Score on entry of ≥ 6.5 than in patients with a < 6.5 value. Our data indicate that early pathophysiological studies augment the clinical information and should be taken into account in the design and analysis of therapeutic trials of acute ischemic stroke.