Previous studies from our laboratory have shown the ME7 model of murine scrapie to be accompanied by an atypical inflammatory response that is characterized by marked astroglial and microglial activation but also by the lack of significant expression of the pro‐inflammatory cytokines interleukin (IL)‐1β and IL‐6. The aim of this study was to determine whether, in the absence of IL‐1β and IL‐6, tumour necrosis factor (TNF)‐α may play an equivalent pro‐inflammatory role, or if an anti‐inflammatory cytokine profile dominates. We have used competitive polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay (ELISA) to determine the levels of TNF‐α, IL‐10 and transforming growth factor (TGF)‐β1 in the ME7 model, using their expression in lipopolysaccharide (LPS)‐induced acute inflammation as a positive control. Levels of mRNA were elevated for all three cytokines during acute inflammation, while TGF‐β1 mRNA alone was significantly elevated in ME7‐injected brains. Similarly, by ELISA, we detected elevated IL‐10, TNF‐α and TGF‐β1 in LPS‐injected animals but only significant elevation of TGF‐β1 in ME7‐injected animals. An increase in laminin and collagen IV deposition around blood vessels was also observed and is consistent with up‐regulation by active TGF‐β1. These findings suggest that TGF‐β1 may play a central role in maintenance of an atypical microglial phenotype and may also be involved in vascular and extracellular matrix changes.