The present study investigated whether the endogenous vasodilating neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) contribute to pial arteriolar vasodilatation in the early phase of pneumococcal meningitis in the rat. Using a closed cranial window preparation we measured the diameters of pial arterioles during 4 h after pneumococcal infection. Arteriolar vasodilatation in infected rats was significantly attenuated by pretreatment with the SP-antagonist spantide up to 3 h after infection. Neither post-treatment with spantide (administered 2 h after infection) nor pretreatment with the CGRP antagonist CGRP(8-37) affected the pneumococci-induced pial arteriolar dilatation. These data suggest that SP is involved as a mediator in early pneumococci-induced dilatation of pial arterioles.