The aims of this study were to investigate the presence of gammadelta T cells in normal human skin, and the possible role of these cells in cutaneous reactions. Twenty-eight samples of normal skin from various sites, and 52 biopsies from inflammatory and neoplastic skin conditions were investigated by immunohistochemical techniques. In normal human skin gammadelta T cells were infrequently seen in the epidermis and dermis. In the inflammatory and neoplastic dermatoses, gammadelta T cells were occasionally present, accounting for 0-5% of CD3+ cells in most of the biopsies examined. In one case of pityriasis lichenoides chronica and one case of lichen planus gammadelta T cells were found to be increased, accounting for 15% of the CD3+ cells in each case. Dermal gammadelta T cells were markedly increased in three of six cases of Langerhans cell histiocytosis, with up to 3 0% of dermal CD3+ cells showing positive staining to an anti-T-cell receptor gammadelta monoclonal antibody. In two of these cases gammadelta T cells were seen in both the dermis and the epidermis. In two further cases dermal gammadelta T cells were not a prominent feature, but small clusters of epidermal gammadelta T cells were observed. T cells bearing the gammadelta T-cell receptor are thus not a major feature of normal human epidermis, unlike the murine system, where the great majority of epidermal lymphocytes express the gammadelta T-cell receptor. The finding of numerous gammadelta T cells in Langerhans cell histiocytosis suggests a possible functional relationship between gammadelta T cells and Langerhans cells or possibly a pathogenic role of these cells in Langerhans cell histiocytosis.