To study the thrombolytic effect of tissue plasminogen activator (t-PA) on cerebral emboli, we characterized cerebral embolization in stroke-prone spontaneously hypertensive rats (SHRSPs) and Wistar Kyoto rats (WKYs). [125I]Fibrin clot particles (20-100 microns diameter) were injected twice at an interval of 90 min into the left internal carotid artery of WKYs and SHRSPs. After each injection, spontaneous embolus dissolution was monitored with a gamma-ray detector placed on the head of the embolic rats. Embolus dissolution was spontaneously generated in 15 min after the injection of fibrin clots. In WKYs, 21% and 42% of the clots were dissolved 30 and 90 min after the second embolization, respectively. On the other hand, the spontaneous embolus dissolution in SHRSPs was significantly lower than that of WKYs, indicating that the endogenous fibrinolytic ability of SHRSPs is less potent than that of normotensive rats. The intravenous administration of t-PA at doses of 75, 250 and 750 micrograms/kg caused a dose-dependent embolus dissolution in SHRSPs. Furthermore, systematically applied t-PA produced embolus dissolution without causing systemic plasminogen activation, fibrinogen breakdown or bleeding. In conclusion, the intravenous administration of t-PA produces selective embolus dissolution without systemic fibrino(geno)lysis in a cerebral embolic SHRSP.