A total of ninety-four biopsies from normal skin, benign dermatoses, and lesions of human T cell lymphotropic virus type I (HTLV-I)-positive and -negative cutaneous T cell disorders have been examined immunohistologically for reactivity with anti-Tac (monoclonal anti-T cell growth factor receptor). Tac-positive T cells were plentiful in approximately half the specimens, and they were equally frequent in benign and malignant disorders and in HTLV-I-positive and -negative cutaneous T cell disorders. Furthermore, in diseased skin, reactivity with anti-Tac was not confined to T lymphocytes, since it was also a property of dermal macrophages and Langerhans cells, as shown by examination of serial and/or double-stained sections. Comparison with other markers linked to T cell activation and proliferation (i.e., HLA-DR, OKT10 antigen, transferrin receptor, and the Ki-67 nuclear antigen) showed that Tac-antigen expression did not correlate clearly with any of these markers. These data indicate that anti-Tac forms a useful supplement to other monoclonal antibodies for the identification of activated cell subsets in cutaneous lymphoid infiltrates, but they also show that the use of this reagent on cutaneous biopsy specimens is of only limited diagnostic value.