We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.