Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene–related peptide (CGRP) were seen in the adventitia or at the adventitia–media border of the human temporal artery. Pharmacological experiments on isolated temporal artery segments revealed that NPY potentiated the vasoconstrictor responses to noradrenaline, but had no vasoconstrictor ability or only a small vasoconstrictor ability per se. VIP, peptide histidine methionine 27 (PHM-27), SP, neurokinin A (NKA), and CGRP potently relaxed vessels precontracted by prostaglandin F, the relative potency being CGRP > SP > NKA [BOND] VIP [BOND] PHM-27. The amount of relaxation varied between 67 and 91% of the prostaglandin F–induced contraction. The peptide effects were not antagonized by classic adrenergic or cholinergic blockers, suggesting interactions via separate receptor sites.