The authors applied a battery of monoclonal antibodies to T cells and other hematolymphoid cells on frozen tissue sections of lymph nodes with involvement by MF and DL, both with and without a history of MF. All 13 lymph nodes showing histologic involvement with MF showed immunophenotypic abnormalities. All of these cases showed significant loss of Leu-9 expression, and 10 cases showed significant loss of Leu-8 expression. In addition, occasional cases showed loss of the pan-T-cell markers Leu-1, 4, and 5. All cases of DL of histologic grade LN-0 or 1, with or without a history of MF, showed a predominance of T helper cells in paracortical regions without evidence of immunophenotypic abnormalities. Three of the 4 cases of DL of histologic grade LN-2 or 3 showed significant loss of Leu-8 and/or Leu-9 expression identified by a decrease in the ratio of paracortical Leu-8/Leu-4 or Leu-9/Leu-4-expressing cells, all cases with a history of possible or definite MF. These results raise the possibility that the immunologic methods employed may be able to identify cases of DL with early involvement by MF.