Pial microvessels have commonly been used as model systems for studyin
g blood-brain barrier (BBB) properties instead of cerebral cortical mi
crovessels. Since pial microvessels are relatively accessible they hav
e been especially employed in electrophysiological and pharmacological
studies. Measurements of electrical resistance across endothelial cel
ls (EC) as a measure of their barrier properties have been made exclus
ively from pial microvessels in in vivo BBB studies. Similarly the obs
erved responses of microvessels to the application of pharmacological
agents have commonly been made on pial microvessels as representative
of BBB vasculature. In this review the properties of pial and cerebral
microvessels are compared to determine whether the use of the pial mi
crovessel as a model for BBB studies is valid. Similarities are descri
bed in their ultrastructural features, permeability to electron dense
tracers and molecular characteristics. Measurements of electrical resi
stance from pial microvessels are compared with measurements from cere
bral EC monolayers in tissue culture and indirect determinations for c
erebral microvessels in situ. Two notable differences between pial and
cerebral microvessels are described in the adult nervous system. Tigh
t junctions between cerebral EC appear to consist of a uniform populat
ion. In pial microvessels however tight junctions consist of two popul
ations, in one the inter-EC tight junctions resemble those between cer
ebral EC, with fusion of adjacent EC membranes. in the second populati
on the inter-EC tight junctions differ with a discernible gap between
adjacent EC membranes. The distribution of the endothelial barrier ant
igen (EBA) is uniform between EC of cerebral microvessels. By contrast
EC of pial microvessels form a heterogeneous population for EBA expre
ssion which is related to the proximity of the EC to the astrocytic gl
ia limitans. The role of astrocytes in the induction and maintenance o
f the BBB characteristics is briefly reviewed. The possible significan
ce of the lack of an astrocytic ensheathment of pial microvessels is a
ssessed. In summary, caution is urged in employing pial microvessels i
n BBB studies and the need for more information on possible pial micro
vessel heterogeneity is stressed.