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 less than 0.05), based on mortality data and the Canadian Neurological Scale. The 30-day mortality rate was 25%. Survival was significantly better (P less than 0.01) in patients with a Canadian Neurological Score on entry of greater than or equal to 6.5 than in patients with a less than 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.