Leukosialin (Ly 48) is a sialoprotein expressed by bone marrow-derived cells early in their development. To determine whether Ly 48 is expressed by specific subsets of epidermal cells (ECs) such as Langerhans cells, keratinocytes, or dendritic epidermal T cells (DETCs), we utilized flow cytometry to detect staining of ECs by a panel of four monoclonal antibodies (S11, S15, S7, and 3E8) that recognize two different epitopes of the leukosialin antigen. Approximately 2.0% of unfractionated ECs expressed Ly 48, as demonstrated by reactivity with the monoclonal antibodies S11 and S15. Similarly, immunoblots of unfractionated EC lysates revealed an antigen of 125 kD apparent molecular weight that reacted with the S11 monoclonal antibody. Enrichment or depletion of various EC populations indicated that DETCs are the only EC population that express Ly 48. Studies of long-term cultured DETC lines indicated a marked heterogeneity of expression of Ly 48 epitopes. The function(s) of Ly 48 on DETCs as well as T-cell receptor alpha/beta bearing mouse T cells remains to be determined.