Treatment of brain microvessels with endothelin-1 evoked an early decrease in the sphingomyelin levels concomitantly with an increase in those of ceramides. These responses were time- and concentration-dependent. Evidence also shows that endothelin type A receptors are involved. This is the first report on the involvement of an agonist in the regulation of the ceramide signal transduction system on blood-brain barrier and shows a new pathway likely involved in the regulation of the cerebral microvascular functioning. (C) 2003 Elsevier Science (USA). All rights reserved.