In this report, we examined interferon-gamma (IFN-gamma) and interleukin-1 beta (IL-1 beta)-mediated regulation of the expression of C3, the third component of complement, in a human astroglioma cell line. Interleukin-1 beta induced C3 protein expression ten-fold more rapidly than IFN-gamma. De novo protein synthesis was required for IFN-gamma to stimulate C3 expression, while cycloheximide and IL-1 beta treatment of cells markedly increased C3 expression. Actinomycin D, inhibited C3 gene induction by IFN-gamma and IL-1 beta suggesting that these cytokines act, in part, at the transcriptional level to enhance C3 expression. Understanding cytokine-mediated regulation of complement gene expression in the astrocyte is important in defining the role of these molecules in CNS inflammation and autoimmune diseases.