Tight junctions between cerebral endothelial cells and the near absence of pinocytosis and vesicular transport of blood-borne protein into and across these cells are believed to constitute the mammalian blood-brain barrier. In the present investigation evidence is provided to indicate that the capillary endothelium of the mouse brain pinocytosis the enzymatic tracer horseradish peroxidase (EC 1.11.1.17) from cerebral blood under normal conditions. This protein and the internalized endothelial surface membrane associated with it are directed, for the most part, to acid hydrolase-positive lysosomes for degradation. Although peroxidase was never seen in the perivascular clefts, the lysosomes of pericytes were peroxidase-positive. Pericytes are macrophage-like cells located on the abluminal surfaces of cerebral microvasculature; these cells may serve as the first line of defense once the blood-brain barrier is breached. The definition of the blood-brain barrier should be expanded to include consideration of the lysosomal system of organelles in endothelial cells and pericytes.