Lm-1 is an Igh-linked locus that codes for cell surface alloantigens (Lm-1 determinants) recognized by T lymphocytes. Using Lm-1 congenic strains and cold-target inhibition of anti-Lm-1-specific lysis by cytotoxic T lymphocytes, we were able to demonstrate differential expression of two distinct Lm-1 antigenic determinants. One determinant is expressed on the surface of T cell blasts, the other on a number of pre-B cell lines. Both determinants are present on B cell blasts. Macrophages also bear Lm-1 determinants, and possibly express a determinant not found on lymphocytes. Fibroblasts, (unstimulated) thymocytes, and immature T cells lack detectable Lm-1 determinants. These data indicate that expression of the Lm-1 locus is dependent on cell lineage and the stage of cell differentiation or activation. We propose that Lm-1 is a lymphocyte-macrophage differentiation locus containing a number of structurally and functionally related genes. Evidence was presented that Lm-1 may also serve as a histocompatibility locus of major importance for bone marrow transplantation. Specifically, when Lm-1-incompatible bone marrow cells and spleen cells (from normal or anti-Lm-1 immune mice) were transplanted into X-irradiated recipients, the maturation and/or function of bone marrow-derived donor B cells was delayed or inhibited.