Inflammation in the central nervous system (CNS) can be studied in experimental autoimmune encephalomyelitis (EAE). The proinflammatory cytokines interferon-gamma (IFN-γ) and tumour necrosis factor (TNF) are implicated in EAE pathogenesis. Signals through the type 1 TNF receptor (TNFR1) are required for severe EAE to develop, whereas deficiency in IFN-γ or its receptor result in more severe EAE. We investigated IFN-γ expression in TNFR1-deficient (TNFR1–/–) mice. We describe here that there were more IFN-γ-secreting T cells present in the CNS of TNFR1–/– mice during EAE compared to wild-type (WT) mice, despite that clinical symptoms were mild, with delayed onset. There was greater expression of IL-12/23p40 by antigen-presenting cells in these mice, and in vitro, TNFR1–/– antigen-presenting cells induced greater secretion of IFN-γ but not interleukin (IL)-17 when cultured with primed T cells than did WT antigen presenting cells. TNFR1–/– mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE. These data demonstrate that IFN-γ expression is enhanced in the CNS of TNFR1–/– mice with EAE and suggest that IFN-γ levels do not necessarily correlate with EAE severity.