Rapid passage of horseradish peroxidase (HRP) from the blood circulation to the cerebrospinal fluid was demonstrated in postnatal rats. At 30 min-1 h after an intravenous (i.v.) injection of HRP, the extravasated tracer from the blood vessels entered the connective tissue of the choroid plexus to reach the epithelial intercellular spaces where it was retarded by the apical tight junctions. The HRP which accumulated in widened intercellular spaces was readily endocytosed by the epithelial cells, notably at their lateral surfaces. This was especially pronounced 3 h after the injection. The endocytosed HRP was either routed to lysosomes or discharged apically by exocytosis into the CSF via membrane-bound vesicles by the epithelial cells. After longer survival periods, i.e. 6 h after injection, the intercellular spaces were relatively clear of tracer. HRP-labelled vacuoles or vesicles had diminished with a concomitant increase in the number of lysosomes containing HRP reaction product. In the course of HRP injection, the epiplexus cells residing on the choroid epithelium progressively accumulated HRP by endocytosis so that in rats killed 6 h after injection, the cells were heavily loaded with HRP incorporated into massive lysosomes. The labelling pattern of epithelial and epiplexus cells in rats injected intraperitoneally followed that observed in those receiving i.v. injections. These results suggest that the epiplexus cells together with lysosomal activity by the choroid epithelial cells serve as a protective line of defence for the blood-CSF barrier which appears to be inefficient.