The vascular effects of endogenous substances can be easily studied in the skin. Early in this century, vasoregulation was shown to be dependent on innervation. Peptidergic transmitters have been shown to co-exist and co-transmit along with nonadrenalin and acetylcholine, sometimes being responsible for nonadrenergic-noncholinergic responses. This review summarizes recent information on vasoregulatory effects of neuropeptides such as substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), neuropeptide Y (NPY), and somatostatin. All these peptides are vasodilators, and some of them seem to be involved in neurogenic inflammation. Some vasoactive peptides and other vasoactive molecules, such as nitric oxide (NO) and histamine, can originate both from nerves and cells and are crucially involved in vasoregulation. Other cell-derived peptides and molecules, such as bradykinin, endothelins, and prostaglandins, may contribute to neurogenic inflammation. All the peptides and molecules described also exist in other organs such as the brain, heart, lung, pancreas, and gastrointestinal tract. The effect of neuropeptides seems to vary from one organ or tissue to another, e.g., NPY is a potent vasoconstrictor in cardiac and cerebral vascular beds but acts as a vasodilator when it occurs in the skin. The presence of mast cells and inflammatory cells may create a special environment in the skin.