The effect of intrathecal tissue plasminogen activator administered at times from 0 to 72 hours after subarachnoid hemorrhage on the development of cerebral vasospasm in primates was examined. Thirty monkeys were randomly assigned into one of five equal groups: a control group that underwent subarachnoid hemorrhage alone, and 0-, 24-, 48-, and 72-hour treatment groups that received 0.75 mg of tissue plasminogen activator at those times after baseline cerebral angiography and subarachnoid hemorrhage on the right side. Seven days later angiography was repeated and the animals were killed. One animal in the 72-hour group developed a delayed ischemic deficit on Day 7 after subarachnoid hemorrhage. In the control and 72-hour groups significant vasospasm occurred in most of the major, right cerebral arteries (P less than 0.05), but no significant vasospasm developed in the 0-, 24-, and 48-hour groups. Although a large subarachnoid clot remained in the control animals, most clot had been dissolved in all treatment groups. Lysing of subarachnoid hematoma with intrathecal tissue plasminogen activator within 72 hours of subarachnoid hemorrhage is effective in preventing vasospasm in primates.