The author has investigated the protective effects of systemic Heparin and intrathecal Urokinase in the multi-hemorrhage canine model of severe chronic cerebral vasospasm. Each of 20 adult mongrel dogs was assigned to one of three experimental groups. All animals received a total of 12ml of fresh unheparinized autologous blood via three cisternal injections. Selective vertebral angiograms were obtained before and 8 days after the initial subarachnoid blood injection. Seven animals were treated by systemic Heparin for 7 days, the other seven were treated by intracisternal Urokinase for 3 days, and the remaining were not treated. Comparisons were based on the percentage of reduction in basilar artery diameter(% RBAD). The ultrastructural changes were studied by transmission electron microscopy(TEM). There was a mean reduction(+/-standard deviation) of 65+/-7% in control dogs, 53+/-5% in dogs with systemic Heparin(difference significant t-test, p<0.01), 37+/-6% in dogs with intrathecal Urokinase(difference signignificant, t-test, p<0.01). The preventive effects of intrathecal Urokinase was superior to systemic Heparin. There was a stroung trend toward reduction of medial necrosis in the basilar artery in dogs with intrathecal Urokinase(p<0.01), and with systemic Heparin(0.05 Adult ; Angiography ; Animals ; Arteries ; Basilar Artery ; Dogs ; Heparin* ; Humans ; Muscle, Smooth ; Necrosis ; Urokinase-Type Plasminogen Activator* ; Vasospasm, Intracranial*