Technical Abstract: The Cattle Fever Tick Eradication Program (CFTEP) has successfully prevented the establishment of the cattle fever tick (CFT) and the southern cattle tick in the U.S since 1943. However, the emergence of acaricide-resistant ticks in many areas of Mexico puts the continued success of the CFTEP at serious risk. Anti-tick vaccines (recombinant Bm86) are a control technology used in conjunction with strategic application of acaricides in integrated control programs implemented in regions of the world where CFT are endemic. This technology could be beneficial to the CFTEP. A considerable body of literature is available regarding the bovine immune response and anti-tick efficacy of Bm86-based vaccines, whether formulated as the Australian TickGardTM or as the Cuban Gavac®, but these products have never been tested in the U.S. For reasons that remain to be fully understood, BM86-based vaccines are more efficacious against Rhipicephalus annulatus than on R. microplus. In studies completed in Mexico, Gavac has achieved 60-80% and 99.9-100% control of R. microplus and R. annulatus, respectively. Interestingly, vaccination in combination with macrocylic lactone (ML) treatment has been reported to be synergistic. The effective duration of a single injection of ML in combination with vaccination was 3 times that of the ML used alone, 12 versus 38 days, respectively. In this study we plan to evaluate the efficacy of Gavac using R. microplus and R. annulatus collected in the United States to assess the utility of BM86-based vaccines as part of sustainable eradication efforts by the CFTEP.