The neurohumoral modulation of the permeability increasing effect of histamine was studied in pigeon skin. Substances were administered through plasmapheresis capillaries inserted into the dorsal wing skin and the protein contents of the perfusates were determined by a quantitative method. The vascular labelling technique was also utilized to histologically identify leaky blood vessels. In the innervated skin histamine evoked a significant, dose-dependent plasma extravasation which was markedly augmented by the coadministration of a specific galanin receptor antagonist, galanin-1-16-bradykinin-2-9-amide (M35). Chronic cutaneous denervation per se resulted in a significant elevation of the permeability-enhancing effect of histamine. In the denervated skin this response was not affected by M35 but was significantly inhibited by galanin. It is concluded that in the normally innervated skin endogenous galanin may exert a neurogenic tonic inhibitory effect on histamine-induced plasma leakage. It is suggested that sensory nerves possess not only pro-inflammatory, but also anti-inflammatory (inhibitory) sensory-efferent functions.