After intravenous injection, cytochrome c does not enter the cerebrospinal fluid. In most areas of the brain, the marker is prevented from leaving cerebral vessels by the capillary endothelium. In the choroid plexus, the marker passes freely out of capillaries into the extracellular space. However, it does not traverse tight junctions between epithelial cells and is rapidly incorporated into mnembrane-bound vesicles within the cell cytoplasm. Thereafter, cytochrome c is apparently removed by lysosomal degradation. These data suggest that there are at least two morphologically distinct blood-brain barriers to cytochrome c and that pinocytosis may be a mechanism for intracellular degradation rather than transcellular transport.