TGF-β is a widely expressed immunoregulatory protein that exerts a diverse range of effects on many types of cells. One of the effects of TGF- β is the inhibition of both constitutive and cytokine-inducible class II MHC gene expression. In this study, we demonstrate that TGF-β inhibits expression of class II MHC surface protein, mRNA, and promoter activity in primary astrocytes, and that this inhibition is both dose and time dependent. TGF-β does not act to inhibit IFN-γ-induced gene expression in a global fashion, as induction of ICAM-1 and IRF-1 gene expression by IFN-γ is unaffected by treatment with TGF-β. Furthermore, TGF-β does not affect events that are involved in IFN-γ-induced intracellular signaling such as tyrosine phosphorylation of JAK1, JAK2, and STAT1α, nor does it affect IFN- γ induction of the class II X2 box binding protein IFN-γ enhanced factor X. We speculate that TGF-β may be exerting its effects by modulating the expression or function of constitutively expressed factors responsible for regulation of class II MHC gene expression in astrocytes.