We describe a model of thromboembolic stroke in rabbits that utilizes the Seldinger technique and digital arteriography. The internal carotid arteries of 14 rabbits were catheterized selectively and embolized with autologous blood clots. After embolization, eight rabbits received IV tissue plasminogen activator (tPA); the remaining six were infused with saline and served as controls. After embolization, cerebral arteriograms were obtained at 30-min intervals for 180 min. Cerebral arteriograms obtained after tPA therapy revealed partial or complete thrombus dissolution in seven (88%) of the eight treated rabbits. In the control group, none of the arteriograms of the embolized internal carotid arteries showed thrombus dissolution. In the tPA-treated group, the median time for thrombus dissolution was 60 min. This stroke model is economical, reproducible, and less traumatic to the brain than most of the previously described animal models. It also provides a means to compare the safety and efficacy of various thrombolytic agents in small animals.