The morphology of the normal blood-brain barrier in the rabbit by thin sect
ion and freeze-fracture electron microscopy is reported. Exogenous tracer h
orseradish peroxidase was injected to visualize the integrity of the blood-
brain barrier in New Zealand White rabbits. Freeze-fracture was used to det
ermine the intramembrane architecture of the tight junctions. Thin sections
(60-100 nm) of brain capillaries from animals injected with horseradish pe
roxidase (HRP) possessed few pinocytotic vesicles in the cytoplasm. Junctio
nal profiles between adjoining plasma membranes were present. Thin sections
of capillaries containing electron dense HRP reaction product (HRP-RP) in
the lumen revealed focal fusions of apposing plasma membranes that occluded
reaction product from entering the junctional clefts. Some cytoplasmic ves
icles were filled with HRP-RP; however, basal laminae and brain interstitiu
m were free of HRP-RP in all vessel profiles examined. Freeze-fracture elec
tron microscopy revealed tight junctions as an elaborate network of interco
nnecting strands of intramembrane particles appearing as ridges on the EF f
ace and corresponding grooves on the PF face on platinum replicas. Results
of this study demonstrate the architecture of rabbit brain microvessel endo
thelial junctions (blood-brain barrier) and provide evidence that the tight
junctions prevent HRP extravasation. It is concluded that rabbit brain end
othelial tight junctions (zonulae occludentes), as in other mammals, form t
he anatomical basis of the blood-brain barrier. Consequently, the rabbit br
ain microvasculature can be a useful model for establishing stereotactic ra
diosurgical procedures to treat brain astrocytomas (tumours).