Lymphomatoid papulosis (LyP) is characterized by the presence of large multinucleated cells resembling Reed-Sternberg (RS) cells. Evidence of antigenic similarity between these two cell types has been sought by immunohistologic labeling of 10 biopsies from cases of LyP with monoclonal antibodies against Ki-1 and other RS and Hodgkin (H) cell-associated antigens. In all cases studied, a proportion of the large atypical cells expressed the Ki-1 antigen. On the contrary, in 20 biopsies of benign skin lesions or cutaneous T-cell lymphomas, Ki-1-positive cells were absent or only occasionally present. Furthermore the large atypical cells of LyP also expressed antigens (e.g., T3, T4, HLA-DR, IL-2 receptors) which we have previously demonstrated on RS cells in the majority of cases of Hodgkin's disease (HD). These findings, in conjunction with the observation that Ki-1 antigen expression can be induced on peripheral blood lymphocytes following exposure to phytohemagglutinin or HTLV I, provide evidence that the Ki-1 positive cells in LyP represent activated T cells as RS cells do in many cases of HD.