Studies in mice have revealed considerable strain variation in the agents causing transmissible spongiform encephalopathies (TSEs). TSE strains interact with genetic factors in the host (in particular PrP genotype) to influence characteristics of the disease such as incubation period and neuropathology. TSE strains can retain their identity after propagation in different host species or PrP genotypes, showing that these agents carry their own strain-specific information. It is not known whether this information resides in specific self-perpetuating modifications of PrP, or whether a separate informational molecule is required. Strain typing in mice can be used to explore links between TSEs occurring naturally in different species. Such studies have demonstrated that the strain causing BSE in cattle has also infected domestic cats and exotic ungulates. Most importantly, the BSE strain has also been isolated from patients with variant CJD. In contrast, different TSE strains are associated with sporadic CJD and sheep scrapie.