γ-Immune protein-10 (γ-IP10) is a cytoldne whose expression has been shown to be induced by interferon-γ. It is a member of a group of closely related cytoldnes (e.g., interleukin 8 and platelet factor 4) with chemotactic properties. γ-IPIO has been detected in keratinocytes, lymphocytes, monocytes, and endothelial cells in immunologically mediated processes, such as positive tuberculin skin tests, and in growth-activated keratinocytes, such as in psoriasis. Keratinocytes in normal epidermis do not produce γ-IP10. We tested the hypothesis that keratinocytes adjacent to dysplastic nevi and melanomas would produce γ-IP10, perhaps as part of an immune response to a tumor, and that this response would not be seen in ordinary melanocytic nevi. We used an affinity-purified, polyclonal rabbit anti-γ-IP10 antibody to examine 10 nevi with moderate to severe histologic dysplasia, one superficial spreading melanoma, and 10 compound melanocytic nevi with no features of dysplasia. As predicted, keratinocytes surrounding all of the cytologically atypical melanocytic lesions displayed strong staining with γ-IPI0. There was no staining of keratinocytes adjacent to ordinary melanocytic nevi. The observed keratinocyte staining with γ-IP10 may be related to a host immune response to antigenically abnormal cells.