Time course of plasma extravasation in neurogenic inflammation elicited by histamine iontophoresis and topical capsaicin application was measured in vivo by a modified intradermal microdialysis technique in humans. Single linear plasmapheresis fibers were inserted intracutaneously at the volar forearm and perfused with Ringer's solution (4 microl/min) with one microdialysis fiber located at the planned stimulation site and a second inside the axon reflex area. Protein concentration in the dialysate increased by 300% in the histamine wheal but no increase was found in the surrounding flare area. There was no protein extravasation in the skin treated with capsaicin nor in the surrounding flare region. Inside the histamine-induced flare reaction a significant increase of calcitonin gene related peptide (CGRP) was found, whereas the increase of substance P (SP) was not significant.