Twenty Hereford heifers approximately 9 months of age were vaccinated with saline (control) or 2 ؋ 10 10 CFU of the Brucella abortus strain RB51 (RB51) vaccine. Immunologic responses after inoculation demonstrated significantly greater (P < 0.05) antibody and proliferative responses to RB51 antigens in cattle vaccinated with RB51 than in the controls. Pregnant cattle received a conjunctival challenge at approximately 6 months of gestation with 10 7 CFU of B. suis bv. 1 strains isolated from naturally infected cattle. The fluorescence polarization assay and the buffered acid plate agglutination test had the highest sensitivities in detecting B. suis-infected cattle between 2 and 12 weeks after experimental infection. Serologic responses and lymphocyte proliferative responses to B. suis antigens did not differ between control and RB51 vaccinees after experimental infection. No abortions occurred in cattle in either treatment group after challenge, although there appeared to be an increased incidence of retained placenta after parturition in both the control and the RB51 vaccination treatment groups. Our data suggest that the mammary gland is a preferred site for B. suis localization in cattle. Vaccination with RB51 did not reduce B. suis infection rates in maternal or fetal tissues. In conclusion, although B. suis is unlikely to cause abortions and fetal losses in cattle, our data suggest that RB51 vaccination will not protect cattle against B. suis infection after exposure.The United States declared that all cattle in all states are free from Brucella abortus infections in 2009. The elimination of B. abortus from cattle was the result of national eradication activities that began in 1934, with total costs exceeding $10 million (18). Although several wildlife reservoirs remain a threat for reintroduction, ongoing monitoring activities are designed to detect any events resulting in transmission to domestic cattle (11).Although B. abortus has been eliminated from domestic cattle, the prevalence of B. suis in feral swine has emerged as a significant problem for domestic cattle. Feral swine populations continue to increase in the United States, and illegal transportation continues to expand their range into new states or regions (9). Contact with infected feral swine has led to B. suis infections in a large number of cattle, particularly in the south and southeastern United States. Cattle infected with B. suis test seropositive on brucellosis surveillance tests, and the antibody responses cannot be readily differentiated from those due to infection with B. abortus. At this time, data on the temporal characterization of the serologic responses of cattle after acute infection with B. suis are lacking.In many states, calfhood vaccination with B. abortus strain RB51 (RB51) is still utilized in domestic cattle. However, the efficacy of RB51 vaccination in protecting cattle against B. suis infection is unknown. In this study we characterized the serologic responses of cattle to B. suis infection and compared the pathogenesi...