Activation and proliferation of microglia are common cellular hallmarks in many different pathological processes of the central nervous system. Although a number of colony-stimulating factors enhance microglial proliferation in vitro, little is known about the endogenous mitogens. In the present study we show a strong and selective inhibition of microglial proliferation in the facial nucleus of osteopetrotic (op/op) mice, with a genetic deficiency in biologically active macrophage colony-stimulating factor (MCSF). Posttraumatic activation of adjacent axotomized neurons and reactive astrocytes was not affected, emphasizing the specificity of MCSF as a microglial growth factor.