Tumour necrosis factor (TNF) is well recognised for its role in mediating innate immune responses. However, the mechanisms of TNF that influence the adaptive immune response to viral infections are poorly understood. Over recent years, there has been evidence to suggest a role for TNF in the early phase of infection of ruminants with bovine leukaemia virus (BLV). In this study, we infected TNF(-/-) mice with a plasmid encoding infectious BLV to further elucidate the role of TNF in BLV infection. TaqMan quantitative PCR showed that proviral DNA was present in genomic DNA isolated from spleen cells of TNF(-/-) mice 4 weeks post-infection, whereas it was not detected in wild-type mice. We were not able to detect differences in serum IgM or IgG levels between the TNF(-/-) and wild-type mice, or antibodies to BLV after this short period. In showing that the lack of TNF enables the plasmid encoded BLV to persist longer, and therefore rendering the mice more susceptible to an infection with BLV, the data suggest an important defence function of TNF in the early phase of BLV infection.