. [unreadable] IV rt-PA alone is an effective therapy for acute ischemic stroke but has substantial limitations when used alone in opening occluded major extracranial and intracranial arteries. The EMS and IMS I Pilot Studies (over 120 subjects in controlled pilot trials), as well reported experience at clinical centers, demonstrate that a combined IV and IA approach to recanalization, using rt-PA administered within three hours of onset, is as safe and may have improved efficacy as compared to full-dose IV rt-PA as administered during the NINDS rt-PA Stroke Trial. This current proposal is for a planning grant to complete the remaining steps necessary for the initiation of a Phase III randomized clinical trial - The Interventional Management of Stroke (IMS) III Trial. The Primary Objective for the planned IMS III Trial is to determine if ischemic stroke subjects with a baseline NIH Stroke Scale Score (NIHSSS) >_10 treated with recombinant tissue plasminogen activator (rtPA; Activase (r) [Alteplase recombinant]; Genentech, Inc.) utilizing a combined IV/IA approach to recanatization started within 3 hours of onset, are more likely to have a favorable outcome at 3 months (Rankin 0-2) as compared to subjects treated with standard 1V rt-PA alone. We will use the period of the planning grant to: 1. Recruit and certify additional centers. 2. Finalize the protocol, manual of procedures, and case report forms. 3. Continue to analyze IMS I and IMS II data for Phase III planning. 4. Organize meetings of participants at the neuro-interventional conferences and the International Stroke Conference to update Trial progress. 5. Have interventionalists and critical care physicians compose guidelines to standardize intra-procedural sedation and anesthesia. 6. Prepare training schedules and materials. 7. Establish membership of committees, identify independent medical monitors, and independent contract research monitors. 8. Develop a cost-benefit analysis for a combined IV/IA approach under different assumptions. 9. Prepare the IMS III clinical and accompanying statistical grant proposal with final budget. 10. Explore funding of interventional angiography by CMS. 11. Continue interaction with industry, with attention to devices that might be applied to a device-augmented future IV/IA paradigm. [unreadable] [unreadable]