The surface antigen profile of HEL cells was probed with a panel of monoclonal antibodies that have been associated with various hemopoietic lineages. Although the list of antibodies tested is by no means complete, the following characteristic picture emerges. a. Affiliation of HEL cells with erythroid lineage has been secured by other than the globin criteria. In this respect differences with K562 cells have been mostly of a quantitative nature, with only a few exceptions. One notable exception is the presence of group H determinant in HEL cells. b. There is a strong expression in HEL cells of determinants present in the platelet/megakaryocytic series. K562 cells express only selective determinants for this lineage. c. In contrast to K562 cells, there is a strong expression in HEL cells of monocyte-associated determinants. Corroborating this are the cytochemical properties of the HEL cells [11] and their induction by TPA (12-0-tetradecanoyl-phorbol-13-acetate) to a macrophage-like phenotype [41]. d. Granulocyte-specific antigens have not been found in HEL cells, although shared antigenic determinants of granulocytes with other cells can be expressed. In contrast, K562 cells display several granulocyte-specific antigens. e. No T-cell-associated antigens are found in HEL cells, although some B-cell-associated determinants can be detected. The interpretation of the composite phenotype in HEL cells is, as yet, unclear. One fact stands out, however; the only two erythroid-associated lines available today also display a multilineage-affiliated phenotype that seems to have no parallel with the other cell lines thus far described.