The effects of substance P (SP) and calcitonin gene-related peptide (CGRP) were tested on pial arterioles of mice. This was done because (1) perivascular peptidergic nerves may play an important role in modulation of cerebrovascular responses; (2) there are conflicting data concerning the mechanism of action of CGRP; (3) there are few or no studies directly testing the endothelium dependence of dilation by these peptides in the cerebral circulation; and (4) we wished to extend previous observations of mice by comparing peptidergic responses in the mouse with those published for other species.