Following intravenous injection, cytochrome c traverses the capillary endothelium of the rat choroid plexus and permeates the perivascular space and the extracellular space between epithelial cells. The tracer is incorporated into pinocytotic vesicles adjacent to the lateral and basal plasmalemmas. Thereafter, cytochrome c is incorporated into multivesicular and dense bodies. Tracerladen vesicles were not found to fuse with the apical plasmalemma and cytochrome c was not discharged into the cerebral ventricles. Acid phosphatase activity of the choroidal epithelium after the administration of cytochrome c was greatly increased and localized in the same intracellular sites shown for cytochrome c. These data suggest that cytochrome c and possibly other proteins that penetrate the choroidal stroma are taken up by the choroidal epithelium and subsequently degraded in lysosomal vesicles. This heterolytic mechanism may be an important means for preventing the entry of certain substances such as proteins into CSF and subsequently into nervous tissue.