The acute inflammatory response in the murine CNS is different from that observed in other tissues. Few polymorphonuclear leukocytes are recruited to the brain parenchyma and there is a delay in the recruitment of monocytes. Leukocyte recruitment to sites of inflammation is dependent on adhesion molecules expressed on the endothelium. The atypical kinetics of leukocyte recruitment to the CNS may be the result of deficient or delayed adhesion molecule expression on the cerebral endothelium. Using immunohistochemistry, the present study demonstrates that following the intracranial injection of a proinflammagen, lipopolysaccharide, or following acute neuronal degeneration elicited with kainic acid, the adhesion molecules ICAM-1 and VCAM were readily upregulated on cerebral endothelium in a time course comparable with that demonstrated on non-CNS endothelium. Both molecules were expressed on vessels, irrespective of their size, at 24h after kainic acid or 6 h after lipopolysaccharide injection but leukocyte recruitment was negligible. The expression of ICAM-1 was demonstrated not only on endothelium but also on microglia especially in response to nerve terminal degeneration. PECAM was constitutively expressed at high levels on cerebral endothelium and did not change during brain injury. However, PECAM was induced on astrocytes after lipopolysaccharide injection or during acute neuronal degeneration, the latter providing a particularly strong stimulus. This study indicates that the expression of these adhesion molecules on CNS endothelium is neither deficient or delayed and that they are unlikely to be limiting factors in leukocyte recruitment to the CNS.