Fluosol-DA (Perfluorochemical Blood Substitute) was investigated in a previous study and found to provide some protection from ischemia and possible usefulness in limiting the size of infarction. In the present study, larger doses over longer periods of acute focal cerebral ischemia were used. Twenty four cats had transorbital ligation of the middle cerebral artery (MCA). The 12 experimental animals were given 20% Fluosol-DA. The control group of 12 received isotonic saline solution. Twenty-four hours after the MCA occlusion, the cats were perfused with saline and phosphate-buffered formalin. The brains were removed and immersed in 10% formalin for 2 weeks. The results of macroscopic and histological examination suggested that, although Fluosol-DA did not provide complete protection from ischemic injury to the brains of the cats treated, it may have helped to slow the development of the pathological changes.