Sixteen clinical centers in two countries have undertaken a prospective open angiography- and computed tomography scan-based safety and efficacy dose-rate finding study of recombinant (two-chain) tissue plasminogen activator (rt-PA) in acute thrombotic and thromboembolic stroke. Preliminary experience with 71 rt-PA treated patients in seven dose-rate groups has demonstrated both partial and complete recanalization, documented by angiography, although a dose response has not yet been achieved. Hemorrhagic infarction has been documented at all dose rates, and dose-rate independent cerebral hematomas have been observed. The study continues at higher dose rates while still remaining within the safety guidelines.