Master of PHILOSOPHYFoot-and-mouth disease (FMD) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. In Tanzania the disease is known to be endemic with periodic outbreaks occurring in different geographical areas. This study was conducted to determine the seroprevalence and socio-economic impact of FMD in relation to livestock movements in a wildlife–livestock interface ecosystem (Serengeti and Bunda Districts) compared to a noninterface ecosystem (Iramba and Kongwa Districts). The study attempted to establish the socio-economic impact of FMD in these study districts. Four hundred serum samples were collected from Serengeti (n = 100), Bunda (n = 100), Kongwa (n = 100) and Iramba (n = 100) and tested for FMD antibodies presence using 3ABC-ELISA. In addition, forty questionnaire copies to establish the socio-economic impact of FMD were administered to livestock keepers: Serengeti (n = 10), Bunda (n = 10), Kongwa (n =10) and Iramba (n = 10). Significantly higher association between geographical areas and seroprevalence was recorded in the wildlife-livestock interface areas (71.5%; 143/200) compared to non-interface areas (61.0%; 122/200) (X2 = 4.9308, p = 0.0264, C.F 95%). Socially, FMD outbreaks impact on food insecurity (85.0%), failure to meet education costs (90.0%) and medical costs (77.5%). Economically, FMD impacts were observed in losses associated with treatment costs (87.5%), milk productivity (85.0%), draught power (80.0%), livestock market loss (67.5), lower livestock weight gain (60.0%), lower fertility (37.5%), abortion (35.0%), death of animals (25.0%) and vaccine supply costs (2.5%). In conclusion, FMD is more prevalent at the wildlife-livestock interface (71.5%) than in non-interface areas (61.0%). Higher percentages in case response on social impacts and economic losses indicate magnitude of the problem and feelings of livestock keepers about FMD in both ecosystems. However, lower percentage on case response to vaccine supply cost indicates there is no control of FMD by vaccination.Wellcome Trust Southern African Centre for Infectious Disease Surveillance (SACIDS)