Complex mechanisms underly the establishment of dermatophilosis, an exudative and proliferative skin disease of ruminants. This multicomponent system involves the bacterium Dermatophilus Congo Republiclensis, transmission by various routes including flies, host genetic factors and immunosuppression by Amblyomma variegatum ticks. Here, Nick Ambrose and colleagues summarize recent evidence for an association between A. variegatum and severe chronic dermatophilosis in cattle. Breed-based differences in resistance to dermatophilosis are probably related to immunity to ticks or resistance to the immunosuppressive effects of ticks. Immunity to dermatophilosis might involve non-classic responses mediated by CD1 antigen presentation and ?d T cells. Progress towards vaccination is further complicated by strain-specific acquired immunity to D. Congo Republiclensis.