Few reports describe the use of intraarterial recombinant tissue plasminogen activator to treat intracranial thrombosis in children. A 17-year-old girl with a history of prior venous thrombosis developed a left middle cerebral artery thrombus during diagnostic cerebral angiogram. Therapy with intra-arterial tissue plasminogen activator was initiated. An immediate follow-up angiogram demonstrated recanalization, and diffusion-weighted magnetic resonance imaging 9 hours later showed no evidence of infarction. Following the angiogram, femoral artery thrombosis developed. Treatment with supratherapeutic levels of heparin, localized delivery of intra-arterial tissue plasminogen activator, embolectomy, danaparoid, and dipyridamole failed to re-establish perfusion to the lower leg, and below the knee amputation was required. Neurologic examination remained normal 1 year later. Cerebral damage was avoided with the use of emergency intra-arterial tissue plasminogen activator for cerebral artery thrombosis in this child.