In most regions of the CNS, vascular endothelial cells play an important role in maintaining the composition of the neuronal microenvironment by virtue of their blood-brain barrier (BBB) characteristics. The maintenance of the endothelial BBB phenotype in vitro has been attributed primarily to astrocytes but little attention has been paid the potential role of neurons. In this study we have attempted to injure or destroy neurons and fibers of passage in a circumscribed area while leaving vascular and glial elements intact in order to determine if neurons are involved in BBB maintenance in situ. The immunotoxin OX7-SAP, a conjugate of the Thy-1 antibody OX7 and the ribosome-inactivating protein saporin, was injected into the adult rat striatum to effect neuronal death at the injection site. Although neurons and fibers of passage were destroyed within the lesion, glial cells unexpectedly were also severely injured as determined by immunohistochemical expression of several neuronal and astroglial marker proteins and ultrastructural analysis. The microvasculature remained intact, allowing a qualitative immunohistochemical analysis of several BBB markers at time points ranging from 3 to 28 days postinjection. Despite the loss of both neurons and astroglia within the lesions, the microvasculature continued to express the brain-type endothelial glucose transporter GLUT-1 at all time points examined. In contrast, the barrier to endogenous protein (rat serum albumin) and the expression of endothelial barrier antigen (EBA) decreased initially but recovered even in areas that contained minimal numbers of astroglia and neuronal elements. We conclude that intact neuronal or glial cells do not appear to be necessary for the maintenance in situ of the BBB properties examined herein.