Techniques for selective isolation, labeling, stimulation, and destruction of ameboid microglia allow study of some fundamental questions in neuroimmunology. Examination of surface morphology, proliferative capacity, and cytochemistry suggests that microglia are a class of brain mononuclear phagocytes distinct from blood monocytes, spleen macrophages, or resident peritoneal macrophages. Moreover, cultured ameboid microglia isolated from newborn brain can be induced to grow thin cytoplasmic projections several hundred microns in length; these process-bearing cells resemble a differentiated form of microglia found in adult brain. Ameboid microglia may contribute to brain inflammation by engulfing debris, by releasing cytotoxins, by killing neighboring cells, and by secreting astroglial growth factors. Importantly, ameboid microglia are closely tied to a network of immunomodulators that include colony-stimulating factors and Interleukin-1. The presence of activated microglia during normal embryogenesis and at sites of penetrating brain injury suggests that these cells serve as important effectors linking the immune system with growth and repair of the CNS.