Fixed drug eruptions (FDE) are immunologic reactions to drugs which produce erythematous plaques or blisters that characteristically recur at the same cutaneous sites with repeated anti‐genie challenges. While a detailed pathogenesis of these lesions remains obscure, T‐lymphocyte infiltration has been documented repeatedly. In this study, we tried to determine if FDE were mediated, at least in part, by cytokines, such as gamma‐interferon. We examined biopsies from 6 cases of clinically well‐documented FDE with an HLA‐DR antibody, LN3, and an antibody to gamma IP‐10 (IP‐10), a protein expressed by keratinocytes, monocytes, lymphocytes and endothelial cells following exposure to gamma‐interferon. We found staining of the dermal lymphocytes with anti‐HLA‐DR antibody in all 6 cases examined. Keratinocytes and endothelial cells showed only focal staining at the antibody concentrations used. In addition, there was keratinocyte staining with the IP‐10 antibody at all levels of the epidermis, with accentuation in areas of blister formation. There was more intense staining of keratinocytes with the IP‐10 antibody in cases with accumulations of HLA‐DR positive lymphocytes in the dermis. We believe that these findings are consistent with the hypothesis that FDE represent cell‐mediated immunologic responses to a variety of antigens, and further, that the histologic alterations can be explained, at least in part, by