Basement membrane (BM) composition varies with both blood vessel and with tissue type. Of all BM components, the laminin family shows the greatest variability and represents the biological active component of BMs, interacting with a wide repertoire of integrin and non-integrin receptors to control functions such as vessel integrity and permeability. We will focus on central nervous system (CNS) microvessels, which have a unique composition of cellular and extracellular matrix layers that collectively constitute the blood-brain barrier. In addition to the endothelial cell monolayer and its underlying BM, cerebral microvessels are ensheathed by astrocyte endfeet and leptomeningeal cells, which contribute to a second BM, the so-called parenchymal BM as it delineates the border to the brain parenchyma. At the level of capillaries these two BMs fuse to form a single structure, which shares characteristics of both endothelial and parenchymal BMs. While considerable information is available on the cellular constitutents of the CNS microvessels and their contribution to the BBB, little is known about the BM layers. Our work has shown that endothelial and parenchymal BMs of CNS vessels are structurally and functionally distinct, and has highlighted their importance in the restricted permeability characteristic of the CNS microvessels. In particular, laminin isoforms are heterogeneously localized along the length of CNS microvessels and play an important role in defining sites of high and low penetrability by infiltrating cells, such as extravasating leukocytes during inflammation1. We present data on the biochemical differences of BMs of CNS microvessels, and how vascular laminins provide cues that determine mechanisms of leukocyte penetration of CNS postcapillary venules1. 1. Wu, C., F. Ivars, P. Anderson, R. Hallmann, D. Vestweber, P. Nilsson, H. Robenek, K. Tryggvason, J. Song, E. Korpos, K. Loser, S. Beissert, E. Georges-Labouesse, & L.M. Sorokin. 2009. Nat Med. 15, 519-27