The intradermal application of both mouse and bovine nerve growth factor induced dose-dependently increased vascular permeability as indicated by Evans blue extravasation. Plasma extravasation by nerve growth factor was markedly reduced by capsaicin pretreatment or a combination of H 1- and H 2-histamine antagonists. The finding that biologically inactive nerve growth factor failed to elicit protein leakage indicates that plasma extravasation by nerve growth factor is a characteristic of the biologically active molecule.