The Ly-4 locus defines an alloantigenic specificity present on the surface of lymphocytes of some mouse strains and detected in lymphocytotoxicity tests by an antiserum (BALB/c times SWR)F1 anti-B10.D2. In this paper are presented results which indicate that Ly-4.2 is predominantly represented on B cells and not T cells. In cytotoxicity tests with rabbit complement, the distribution of Ly-4.2 is restricted: thymus 5%, TDL 12%, spleen 60%, lymph node 30%, bone marrow 36%, Peyer's patches 55%, peritoneal exudate cells 35%, and peripheral lymphocytes 35%. This distribution is the reciprocal of that obtained with anti-Thy-1 antiserum. Further, when both reagents were used together, almost all cells in these tissues were lysed, excepting those with bone marrow. When anti-Ly-4.2 and anti-Thy-1.2 were used sequentially, it was apparent that these specificities were present on different cell populations. As Thy-1 is a marker for T cells, Ly-4 is therefore, presumably, a marker for B cells. This conclusion was confirmed by testing mice depleted of T cells ("nude"; thymectomy + anti-lymphocyte serum treatment; thymectomy, irradiation + reconstitution with bone marrow) where the majority of lymphocytes were Ly-4.2+, Thy-1.2-; and by testing tumors, where, for the most part, this reciprocal relationship held true. Appropriate studies indicate that the Ly-4.2 antibody does not detect a surface immunoglobulin allotype. Anti-Ly-4.2 anti-serum may provide a useful alloantigenic marker distinct from immunoglobulin, mouse-specific bone marrow-derived lymphocyte anti;en, and "beta" for detecting some or all, B cells.