British Journal of Dermatology (1983) 109, Supplement 25, 14-17. Peptidergic (neurotensin, VIP, substance P) nerve fibres in the skin. Immunohistochemical evidence of an involvement of neuropeptides in nociception, pruritus and inflammation W.HARTSCHUH, E.WEIHE* AND M.REINECKE* Department of Dermatology, University of Heidelberg, VoiJstr. 2, D-6900 Heidelberg, Germany and *DepartmentofAnatomy III, University ofHeidelberg, Federal Republic of Germany In recent years potent vasoactive effects have been demonstrated in various organs including the skin (Lembeck & Donnerer, 1981) for the biologically active neuropeptides neurotensin (NT), vasoactive intestinal polypeptide (VIP) and substance P (SP) (cf. Hokfelt et al, 1980; Pernow, 1980; Uhl & Snyder, 1980). There is increasing evidence that NT, VIP and SP act as neurotransmitters in some peripheral systems, e.g. NT is a neurotransmitter candidate in the heart (Quirion et al, 1980; Reinecke et al, 1982), VIP probably has neurotransmitter function in the gastrointestinal tract (Fahrenkrug, 1980; Said, Giachetti & Nicosia, 1980) and SP seems to be a transmitter of primary sensory neurons involved in pain perception (Hokfelt et al, 1975; Henry, 1980). In addition, it has recently been shown that SP and, even more potently, KT and VIP cause pruritus after intradermal injection (Hagermark, 1982). To date, SP (Hokfelt et al, 1975). NT (Weihe, Hartschuh & Reinecke, 1981a) and VIP (Weihe et al, 1981b) have been localized immunohistochemicaliy in nerve fibres of the skin only in separate or preliminary studies. However, no histotopographical analysis of the distribution of NT, VIP and SP in the skin has been carried out so far. The present study presents a systematic comparative analysis ofthe localization of these neuropeptides in the skin of several mammalian species, including man. Various regions of human skin (fingertip, arm, axilla, toe tip, prepuce, scrotum, mamilla) and similar regions of some other mammalian species (guinea-pig, rat, cat, dog, monkey) were investigated for the distribution of NT-, VIP-, and SP-immunoreactive (IR) nervefibres.The specimens were dissected, Bouin-fixed and embedded in paraffin. The immunohistochemical reactions were carried out using the peroxidase-antiperoxidase (PAP) technique modified after Forssmann et al. (i98r). The antisera used (anti-NT, code HC-8, donated by Dr S.E.Leeman; Carraway & Leeman, 1976; anti-VIP, code R 501, donated by Dr N.Yanaihara; Dimaline^ Vaillant & Dockray, 1980; anti-SP, code RRF 9/5, own; Reinecke et al, 1982) showed no Correspondence: Dr. Wolfgang Hartschuh, Departmem of Dermatology, University of Heidelbere D-6QO0 Heidelberg, F.R.G. 14