Pathogens that are transmitted between wildlife, livestock and humans present major challenges for the protection of human and animal health, the economic sustainability of agriculture, and the conservation of wildlife. Mycobacterium bovis, the aetiological agent of bovine tuberculosis (TB), is one such pathogen. The incidence of TB in cattle has increased substantially in parts of Great Britain in the past two decades, adversely affecting the livelihoods of cattle farmers and potentially increasing the risks of human exposure. The control of bovine TB in Great Britain is complicated by the involvement of wildlife, particularly badgers (Meles meles), which appear to sustain endemic infection and can transmit TB to cattle. Between 1975 and 1997 over 20,000 badgers were culled as part of British TB control policy, generating conflict between conservation and farming interest groups. Here we present results from a large-scale field trial that indicate that localized badger culling not only fails to control but also seems to increase TB incidence in cattle.