Macrophage precursor cells obtained from murine bone marrow culture supplemented with interleukin-2 (IL-2) are known to possess NK/LAK-like characteristics. In the present work, these cells were tested for their expression of B220 marker on their surface, because the B220 marker was reported as a marker expressed on the activated stages of splenic NK cells. We found that, at the stage with highly lytic activity (LAK-activity), the effector cells derived from bone marrow macrophage precursors do express B220 marker on their surface. This kind of B220 acquisition on the macrophage precursor cells was induced by high-dose interleukin-2, but did not seem to be related with the production of cytosol protein perforin, a cytolytic molecule that can be induced in macrophage precursors upon the stimulation with interleukin-2. On the other hand, a down-regulation of the myeloid markers Mac-1 and F4/80 was observed on the surface of macrophage precursors when the cells began to express B220 marker. As a result, a highly lytic B220+ population lacking myeloid cell markers appeared. Since this population displayed an antigenic profile (B220+ NK-1.1+ CD3– CD8– Thy-1.2+) that is similar to the LAK effectors derived from splenic NK cells, we suggest that this in vitro observed phenotypic variation of bone marrow macrophage precursors during their differentiation under the influence of interleukin-2 may represent the actual developing process of NK/LAK cells, of which the cell lineage has long been remained as unclarified.