Anti-Leu-3a, anti-Leu-3b, OKT4, and anti-T4 murine monoclonal antibodies react with a membrane component expressed by mature peripheral blood helper T cells and certain thymocyte subsets. Using a variety of immunologic staining techniques, we have demonstrated the reactivity of these antibodies with other cell types. Normal and neoplastic cells of monocyte/macrophage lineage bear the Ia+/Leu-6-/Leu-3+ phenotype, whereas histiocytosis X cells bear the Ia+/Leu-6+/Leu-3+ phenotype. The Ia+/Leu-6- cells of malignant histiocytosis and the Ia+/Leu-6+ epidermal Langerhans cells were variably Leu-3+. Normal monocyte/macrophage reactivity with anti-Leu-3/T4 appears to be primarily intracytoplasmic, whereas on U937 monocyte tumor cells, marked membrane reactivity is also observed. These results strongly suggest that certain cells other than helper T cells and thymocytes can express and, at least in some cases, synthesize a component previously regarded as T-lineage specific.