Recent experimental and clinical reports suggest that the intracisternal administration of recombinant tissue plasminogen activator (tPA) within 72 hours of subarachnoid hemorrhage decreases the incidence of severe angiographic and clinical vasospasm. In this report, we present four of eight patients with aneurysmal subarachnoid hemorrhage who developed angiographic and clinical vasospasm with delayed neurological deterioration, despite the use of intracisternal tPA after early aneurysm clipping. One patient did not clear her massive subarachnoid hemorrhage with tPA; one patient had extremely poor collateral flow with occlusion of one cervical internal carotid artery and 80% stenosis of the other cervical internal carotid artery; the other two patients had a subarachnoid hemorrhage 7 to 12 days after their sentinel hemorrhage. Three patients ultimately made excellent or good recoveries, and one was left with hemiparesis. The four other patients treated by this protocol did not develop vasospasm. We conclude that intracisternal tPA may not prevent vasospasm in certain patients. This may relate to inadequate clearing of the subarachnoid clot, pre-existing poor collateral supply, or the occurrence of prior subarachnoid hemorrhage.