Microneurography of human skin nerves has recently contributed detailed information on the peripheral input leading to itch sensations. In this context it has been demonstrated that itch induced by different agents activates different neuronal populations in the PNS. Histamine acts on a specific subgroup of mechano-insensitive C-fibers which are also sensitive to other endogenous mediators, e.g. prostaglandine E2 and acetylcholine, and to capsaicin. Since these agents can also provoke pain, a “selectivity hypothesis” may explain the differentiation between the itch and pain pathways. Though histamine seemed to be the prototypical itch mediator it plays a minor role in part of the clinical itch states. Experimentally, the spicules of mucuna pruriens (cowhage) induce strong non-histaminergic itch. It turned out that they excite an entirely different population of C-fibers, namely mechano-responsive polymodal nociceptor units (CMH) and Adelta units. The neuronal mechanisms of clinically important pruritic states, e.g. in uremia are still unexplored.