Tumor necrosis factor (TNF)-alpha has been postulated to play an important physiologic as well as pathologic role within the developing brain. In the present study, we found that human fetal microglial cells released abundant amounts of TNF-alpha upon stimulation with lipopolysaccharide (LPS). Treatment of microglial cell cultures with antibodies specific to interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta augmented LPS-stimulated release of TNF-alpha. Each of these cytokines dose-dependently suppressed TNF-alpha release. Also, TNF-alpha mRNA expression was inhibited by each of these cytokines. By way of contrast, treatment of microglial cell cultures with IL-alpha or IL-1 beta alone or in the presence of LPS, resulted in increased release of TNF-alpha, and IL-1 stimulated the expression of TNF-alpha mRNA. These findings suggest that these cytokines are likely to modify the beneficial and harmful effects of TNF-alpha within the developing brain.