In this report, we show that in the human astroglioma cell line D54‐MG, both interleukin‐1 (IL‐1β) and tumor necrosis factor‐alpha (TNF‐α) enhance C3 gene expression in a time‐ and dose‐dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30‐fold and 20‐fold in response to IL‐1β or TNF‐α, respectively. C3 protein production increases proportionally, reaching levels 36‐fold and 18‐fold higher than untreated controls upon exposure to IL‐1β or TNF‐α, respectively. D54‐MG cells require a minimal 1 h exposure to IL‐1β in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF‐α. Simultaneous treatment of D54‐MG cells with IL‐1β and interferon‐gamma (IFN‐γ) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF‐α and IFN‐γ. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL‐1β (5.3‐fold increase) and TNF‐α (7‐fold increase), while an additive effect was observed upon simultaneous treatment with both IL‐1β and IFN‐γ. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN‐γ, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis. Copyright © 1993 Wiley‐Liss, Inc.