Activation of microglial cells in neurological diseases involves proliferation and the induction of phagocytic and cytotoxic properties. We studied the effects of four different cytokines on microglial phagocytosis of latex beads to gain further insights into the signals modulating different aspects of microglial activity. Granulocyte/macrophage colony stimulating factor and tumor necrosis factor-alpha enhanced microglial phagocytic activity as measured by flow cytometry. A phagocytosis inhibiting effect was observed after preincubation with transforming growth factor-beta1 and interleukin-4. In conclusion, the activating and deactivating cytokines differentially regulate microglial phagocytic activity in vitro and might also play an important role in vivo in modulating microglial activation to keep the balance between the protective, defensive and destructive, chronic inflammatory properties of microglia.