IL-31 is a T cell cytokine that is preferentially produced by T helper type 2 cells. IL-31 signals through a heterodimeric receptor composed of the IL-31 receptor (IL-31R) and the oncostatin M receptor (OSM). This receptor complex recruits JAK1, JAK2, Stat1, Stat3 and Stat5 signaling pathways, as well as the PI3 kinase/AKT cascade. SHP-2 and Shc adapter molecules are also recruited and contribute to an increased activation of the MAP kinase pathway in response to IL-31. Overexpression of IL-31 in mice results in pruritus and skin dermatitis resembling human atopic dermatitis (AD). Comparisons between skin from patients with AD and healthy skin showed IL-31R expression at higher levels on epidermal keratinocytes in AD samples. Infiltrating cells, more numerous in skin from patients with AD compared with that of healthy individuals, expressed IL-31 mRNA. IL-31 may participate in the cause of itch sensation and promote scratching behavior in NC/Nga mice with atopic dermatitis, and may represent a novel target for antipruritic drug development.