Using an indirect immunoperoxidase technique and a panel of monoclonal antibodies with well-defined specificities, the authors studied the distribution of lymphoid and nonlymphoid cells in the T-cell areas of both involved and uninvolved lymph nodes from patients with mycosis fungoides (MF) and Sézary's syndrome (SS) and dermatopathic lymph nodes from patients with generalized benign skin disease. The distribution of the different T-cell subsets, HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, in the paracortical areas of MF lymph nodes showing features of dermatopathic lymphadenopathy with early involvement, as assessed after conventional histologic examination, was similar to that of dermatopathic MF lymph nodes without early involvement and lymph nodes from patients with generalized benign skin disease, indicating that these studies do not provide additional criteria for the early diagnosis of MF involvement. MF lymph nodes showing partial or complete obliteration of the normal architecture tended to have lower numbers of HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, but showed increased numbers of blast cells, part of which had lost their mature helper-T-cell phenotype. These differences between the early and advanced stages of lymph node involvement by MF were analogous to those observed in the different stages of cutaneous involvement, as described previously. The lymph nodes from patients with SS were diffusely infiltrated by neoplastic T cells that had retained their mature helper-T-cell phenotype (Leu-1+, 3a+, 4+), contained very low numbers of Leu-2+ T-cells and relatively few HLA-DR+ interdigitating cells and OKT6+ Langerhans cells. These different staining patterns in MF and SS lymph nodes may reflect different pathogenetic mechanisms.