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Present study was designed with the objective to find out the sero-prevalence of foot and mouth disease (FMD) in animals and to evaluate the role of FMD vaccination as a control strategy for this disease. Serological analysis of randomly sampled animals (n=373; 110 from Greater Cholistan and 263 from Lesser Cholistan) using nonstructural protein ELISA indicated that 62.2% animals in the Desert had previous exposure to FMD virus. To determine the efficacy of vaccine for prevention of the disease, 7,500 cattle heads located at 131 'tobas' both in Lesser and Greater Cholistan were vaccinated using a trivalent FMD vaccine containing A, Asia-1 and O serotypes. Booster dose was administered after 30 days of primary vaccination followed by immunization after every 6 months. Blood samples were collected at day 0 and at the time of booster dose. Sera samples were analyzed for titres against all 3 serotypes using Solid Phase Competitive Blocking ELISA. At the time of vaccination (day 0), 31.8-64.5% animals showed protective titres indicating previous exposure of animals against all 3 serotypes of the virus. This protective titre further increased from 64% to 87% animals against different serotypes after primary vaccination (day 30). Field observations indicated that after booster dose, none of the vaccinated animals showed any clinical sign of the disease; whereas, FMD outbreaks were recorded in un-vaccinated animals located in the study area. In conclusion, the high quality FMD vaccine, administered following the standard operating procedures, can protect animals against this disease in Desert Production System. [ABSTRACT FROM AUTHOR]