A sheep pox (SP) vaccine (Romanian strain) was inoculated (one and ten doses) into cattle that were subsequently challenge inoculated with a virulent lumpy skin disease (LSD) virus. Vaccinated cattle had markedly reduced lesions compared to non-inoculated controls. In cattle receiving ten sheep doses of vaccine, the duration of LSD lesions was about 15 days compared to approximately 21 days in the cattle given one sheep dose of vaccine. Four out of five cattle inoculated with one dose and four out of five inoculated with ten doses of vaccine were protected from generalized LSD, while, all four nonvaccinated controls experienced generalized LSD following challenge inoculation, one control died. The Romanian strain of sheep pox vaccine induced sufficient cross protective immunity to protect cattle against severe LSD virus challenge. This SP vaccine has the advantage of not being a risk to contact sheep in contrast to situation, where virulent SP is used to immunize cattle against LSD.