The foundation of an acute stroke translational research program is an acute stroke clinical service that will assure maximum patient referral and allow rapid identification, screening and recruitment of potential research subjects in the timely fashion needed to study the early events in cerebral ischemia and enroll patients in acute stroke research protocols. Absence of an emergency department and the time constraints on screening and recruitment of acute stroke patients as research subjects has precluded the NIH Clinical Center as the main site of our research projects. Thus, we have needed to establish and maintain the clinical, imaging and research infrastructure required to support such a program at local hospitals, Suburban Hospital (SH) in Bethesda, Maryland, and Washington Hospital Center (WHC) in DC. The major elements of this infrastructure include the NIH Stroke Service, a combination of NIH and contractor clinicians stroke neurologists, nurses, clinical fellows, on-site research/nurse coordinators, MRI scanners NIH 3T MRI at WHC, shared 1.5 T scanner at SH and MRI technologists, NIH computer network placed and maintained at each hospital, hospital office space for program needs. In addition, we maintain our own PACS for images obtained on the WHC and SH MRI scanners, and developed and maintain a registry for clinical and research patient data. Every year we screen approximately 1200 patients and enroll approximately 100 patients into one of our clinical research protocols. On the NIH campus, we provide experimental stroke models at the NMR center to support our clinical research efforts. For example, using MRI we have developed experimental models of symptomatic intracranial hemorrhage in ischemia-reperfusion and of blood brain barrier disruption on gadolinium-enhanced FLAIR. The experimental MRI signs reproduce those seen on the MRI of acute stroke patients and facilitate the development and translation of novel acute stroke therapies into clinical trials.