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A study to determine seroprevalence and risk factors in transmission of brucellosis at Mikumi-Selous wildlife - livestock interface was carried out. Rose Bengal Plate Test (RBPT) and Competitive Enzyme Linked Immunosorbent Assay (c-ELISA) test were used in this study. Blood samples from 747 cattle, 198 goats, 168 sheep and 60 buffaloes were collected by venipuncture into plain vacutainer tubes. Other opportunistic samples from wild animals were collected from hunters kills and road kill. These include 4 elephants (Loxodonto africana), 6 buffaloes (Syncerus coffer), 6 wildebeests (Connochaetes taurinus), 2 hartebeets (Alcelaphus buselaphus), 4 bushbucks (Tragelaphus scriptus massaicus), 2 reedbucks (Redunca fulvorula), 1 zebra (Equus burchellii), 2 impala (Aepyceros melampus), and 1 sable (Hippotragus niger). Questionnaires were disseminated to 148 pastoralist households to determine risk factors of transmission of the disease in the animal populations.