Thirteen (1.8%) of 708 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I, II and III trials developed a stroke. Four strokes were hemorrhagic and nine were nonhemorrhagic. Of five prespecified risk factors for intracranial hemorrhage (age greater than 65 years, history of hypertension, history of prior cerebrovascular disease, aspirin use and acute hypertension), two patients had two risk factors and one patient had one risk factor. However, 80% of patients without intracranial hemorrhage had at least one risk factor and 31% had two risk factors. No patient with a prior stroke or transient ischemic attack (all greater than 6 months previously) had an intracranial hemorrhage. Of three prespecified risk factors for nonhemorrhagic stroke (atrial fibrillation, prior cerebrovascular disease and large anterior wall infarction), only the occurrence of a large anterior myocardial infarction (with ejection fraction less than 45%) was a predictor (p = 0.0015). The in-hospital death rate was 25% for patients with hemorrhagic stroke versus 11% for patients with a non-hemorrhagic stroke and 6% for those patients without a stroke. Furthermore, the hospital stay was greater than 50% longer in patients who had a stroke than in those who did not. Thus, intracranial hemorrhage remains an unpredictable risk in patients treated with thrombolytic therapy and cerebral infarction is related to anterior myocardial infarction and poor left ventricular function. Both types of stroke are associated with substantial morbidity and mortality.