Global gene expression analysis allows for the identification of transcripts that are differentially regulated during a disease state. Many groups, including our own, have identified hundreds of genes differentially regulated in response to prion infection. Eleven transcripts, upregulated in the brains of prion-infected animals, which were classified in the literature as stimulated by the cytokine interferon-gamma (IFN-γ), were identified. This is intriguing, as IFN-γ has recently been detected in the brains of prion-infected animals. Quantitation of several genes, categorized as IFN-γ inducible, by quantitative real-time polymerase chain reaction (qRT-PCR) confirms that these transcripts are upregulated. Future approaches for delineating the role of IFN-γ-induced transcripts and their function in prion infection are described.