Microglia and astrocytes undergo proliferative and differentiative changes in vivo after trauma or diseases such as multiple sclerosis (MS). Oligodendrocytes are destroyed in lesions in MS. Interleukin-1 (IL1) and tumor necrosis factor-α (TNFα) are involved in inflammation of the central nervous system and are elevated in MS. We have investigated the changes in cell morphology and cell number induced by IL1 and TNFα in purified and mixed populations of primary rat brain microglia, astrocytes, oligodendrocytes, and glial precursors. Depending on the target population, proliferation, differentiation, or inhibition of cultured cells was observed. The data also suggest that interactions among cell populations occur and support the hypothesis that IL1 and TNFα effects may be indirect, possibly through induction of other factors.