Microglial cells are resident immunoeffector cells of the central nervous system. They differ from most other resident macrophages by their ramified shape, their capacity to proliferate, and by a distinct pattern of ion channels. They have therefore been proposed to be a subpopulation of macrophages that arise from a distinct pool of myelomonocytes by early determination of their lineage within the bone marrow. Here we present data which show that distinct properties of the microglial cells are not intrinsic to this subpopulation of macrophages, but are acquired subsequent to their interaction with astroglial cells, since similar properties can be induced in both blood monocytes and spleen macrophages, when these are cultured on astrocytes. These findings add further evidence to the proposition that microglial cells are derived from the myelomonocytic lineage, and also indicate that the properties of resident macrophages are largely determined by tissue components of the host organ.