The Thrombolysis in Pediatric Stroke (TIPS) study is phase I study which will establish the safety, dosing and pharmacokinetics of intravenous (tissue plasminogen activator) tPA for childhood stroke. We propose a five-year international multi-center safety and dose-finding study of intravenous tPA in children with acute arterial ischemic stroke (AIS) to address the overall hypothesis: Intravenous tPA can be given safely to children with acute AIS The primary aim is: To determine, in 36 children treated within 0-4.5 hours of onset of acute arterial ischemic stroke, the maximal safe dose of intravenous (IV) tPA among three escalating doses (0.75. 0.9, 1.0 mg/kg). An adaptive dose finding method will be applied to escalate across the three dose levels within two age groups: 2-10 years (prepubertal) and 11-17 years. Dose will be escalated based on safety (absence of excess toxicity) with at least 3 children treated at each dose level. Intracranial hemorrhage following stroke can occur even in the absence of thrombolytic therapy, but the risk is increased by the use of thrombolytics. In TIPS, toxicity will be symptomatic intracranial hemorrhage (SICH) within 24 hours of tPA. SICH will be defined as a parenchymal hemorrhage involving > 30% of the infarcted area (PH2)6, or an intraventricular, subarachnoid, or parenchymal hemorrhage outside the infarct seen on neuroimaging, associated with a worsening of 4 or more points on the Pediatric adaptation of the NIH Stroke Scale (PedNIHSS) or deterioration in level of consciousness. The two secondary aims are: (1) To measure the pharmacokinetics of tPA, including free tPA, PAI-1, and tPA antigen in children receiving IV tPA for acute AIS. (2) To measure the 3-month neurological outcome in children with acute AIS treated with IV tPA This Phase I study responds to the call by the National Institute of Neurological Disorders and Stroke (NINDS) for collaborative research in childhood stroke. It will establish safety and pharmacokinetics of tPA for childhood AIS, using the International Pediatric Stroke Study (IPSS) group as its infrastructure. Data from this study, including pharmacokinetic data, will form the basis for the investigators to develop and conduct randomized controlled Phase IIb trials to determine the efficacy of tPA in children with AIS, ultimately enabling children who suffer acute stroke to benefit from thrombolysis with tPA, an intervention that has significantly improved stroke outcome in adults.