The recent development of digital subtraction angiography (DSA) has renewed interest in the use of gases, especially carbon dioxide, as contrast agents. Both early physiologic studies and recent clinical reports suggest that arterial CO2-DSA is a safe and useful diagnostic tool in the examination of extremity circulation. The present study examined the neurologic sequelae, pathologic changes, and effects on the blood-brain barrier to intravenous Evans-Blue and horseradish peroxidase of intracarotid CO2, in albino rats. As with other forms of cerebral gas embolization, CO2 produced multifocal ischemic infarctions and disrupted the blood-brain barrier to macromolecular tracers. The site of the barrier lesion is the endothelial cell membrane, although the precise mechanisms of damage remain unknown. Caution must be urged in the use of CO2-DSA to avoid embolization of the central nervous system.