Amoeboid microglial cells (AMC) in the developing brain are active macrophages. The macrophagic nature of these cells has been demonstrated by many methods, such as the localization of various hydrolytic enzymes and the presence of complement type 3 surface receptors in them. More importantly is the direct visualization of these cells engaged in the phagocytosis of degenerating cells at the ultrastructural level. Further evidence of them being active macrophages is the avid internalization of tracers administered by the intravenous or intraperitoneal routes in developing rats. The potential involvement of AMC in immune functions is supported by the induced expression of major histocompatibility complex class I and II antigens on them when challenged by lipopolysaccharide or interferon-gamma. Immunosuppressive drugs, such as glucocorticoids and immune function-enhancing drugs like melatonin, affect the expression of surface receptors and antigens and the release of cytokines by AMC. Recent studies in our laboratory have shown the expression of insulin-like growth factors, endothelins, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and N-methyl-D-asparate receptors. This along with the release of chemokines, such as stromal derived factor-1a and monocyte chemoattractant protein-1, suggests multiple functional roles of AMC in early brain development.