The effect of vasoactive peptides on vascular smooth muscle in the cerebral microcirculation was examined using an isolated intracerebral arteriole preparation. Extraluminally applied vasoactive intestinal peptide (VIP) dilated the spontaneous tone of intracerebral arterioles to 118.9 ± 3.1% of control diameter at pH 7.30, with an EC50 of 7.27 x 10-8 M. Similar degrees of dilation to VIP were seen in vessels preconstricted by changing bath solution to pH 7.60. Substance P had no effect on vessel diameter at pH 7.30. However, in vessels precontracted by pH 7.60, significant dose-dependent dilation was observed with an EC50 of 2.55 x 10-10 M. Neuropeptide Y constricted intracerebral arterioles to 81.22 ± 2.7% of control diameter, with an EC50 of 6.23 x 10-10 M. Bradykinin dilated intracerebral arterioles at pH 7.30 and pH 7.60 to 130 ± 3.0% of control diameter. VIP and bradykinin are potent vasodilators of intracerebral arterioles. Neuropeptide Y is a vasoconstrictor. The effect of substance P appeared to be either pH-dependent or dependent on some degree of precontraction by another agonist, but no effect on vessel diameter was seen at pH 7.30.