Foot-and-mouth disease (FMD) is a contagious viral disease of cloven-hoofed animals, characterised by fever and presence of painful vesicles especially at the mouth, nose and feet. FMD virus exists as seven immunologically distinct serotypes, only serotyp(1) Serum samples collected from 254 sheep in 5 different localities [10th Ramadan (n = 62), Zagazig (n = 58), Abo-Hamad (n =28), Belbis (n = 65) and Menia alkameh (n = 41)] were examined by ELISA for detection of specific antibodies against FMD.The resul(a) 116 (45.66%) and 153 (60.23%) were seropositive against serotype A and O respectively.(b) Seroprevalence of FMD serotype O was higher detected in Belbis (76.92%) followed by Menia alkameh (70.73%); 10th Ramadan (64.51%) and Zagazig (39.45%). The lowest seroprevalence was detected in Abo–Hamad (39.28%).(c) whereas seroprevalence of FMD serotype A was higher in Belbis (76.92%) followed by 10th Ramadan (61.29%); Abo –Hamad (32.14%) and Zagazig (22.41%). The lowest seroprevalence was observed in Menia alkameh (14.63%).(2) Experimental vaccination by bivalent inactivated aluminum hydroxide gel and oil adjuvant (Montanide ISA206) FMD vaccine in sheep.Thirty sheep were used in this experiment and were classified into three groups:• 1st group (10 animals) administrated I/M with 1ml of inactivated oil-adjuvanted FMD vaccine.• 2nd group (10 animals) administrated S/C with 1ml aluminium hydroxide gel inactivated FMD vaccines.• 3rd group (10 animal) non-vaccinated sheep and used as control group.Serum samples were collected from experimentally vaccinated and control sheep weekly interval for 8 weeks then every 2 weeks until disappearance of antibodies. The serum samples were tested serologically by ELISA and SNT.(I) The results of immune response in sheep vaccinated with bivalent inactivated aluminum hydroxide gel vaccine revealed that:(a) Sheep exhibited specific FMD antibodies titers 1.2 log10 by SNT after 2 weeks in one sheep and after 3 weeks in 8 sheep for serotype O and in 7 sheep for serotype A, while all ten vaccinated sheep developed antibodies titer of 1.2 log10 or more after (b) whereas results revealed that vaccinated sheep with the same vaccine exhibited specific FMD antibodies titers one log10 by ELISA after 2 weeks in 5 sheep, while all ten vaccinated sheep developed antibodies titer of one log10 or more after 3 WPV for b(c) FMD serum neutralizing antibodies were peaked at 7 to 8 WPV with maximum mean 1.755 log10 and 1.71 log10 for serotypes O and A respectively. Antibodies were gradually decreased until reached to mean titer (1.275 log10 at 18 WPV) and (1.32 log10 at 16 (d) whereas ELISA results revealed that all vaccinated sheep with the same vaccine showed a maximum mean titer (2.054log10 and 2.059log10) at 8 WPV in serotypes O and A respectively. Antibodies showed gradually decreased until reached mean titer (1.651 lo(e)The duration of protective immunity with aluminum hydroxide gel bivalent (O1 and A/Egypt 2006) inactivated FMD vaccine was 12 - 14 weeks by SNT and ELISA tests respectively.(II) The results of immune response in sheep vaccinated with inactivated bivalent inactivated oil adjuvant (Montanide ISA206) vaccine revealed that.(a) Sheep exhibited specific FMD antibodies titers 1.2 log10 by SNT after 2 weeks in five sheep, while all ten vaccinated sheep developed antibodies titer of 1.2 log10 or more after 3WPV for both serotypes O and A..(b) whereas results revealed that vaccinated sheep with the same vaccine exhibited specific FMD antibodies titers one log10 or more by ELISA after 2 weeks in all vaccinated sheep for both serotypes O and A.(c) FMD serum antibodies by SNT and ELISA reached to the peak level at 12th WPV. Antibodies showed gradually decreased until reached mean titer 1.35 log10 - 1.395 log10 by SNT and 1.699 log10 - 1.652 log10 by ELISA at 32 WPV for serotype A and O respectiv(d) The duration of protective immunity with oil adjuvant Montanide ISA 206 bivalent (O1 and A/Egypt 2006) FMD vaccine was 29-30 weeks by SNT and ELISA tests respectively.CONCLUSION:It could be concluded that:(1) Seroprevalence of FMD infection indicated wide spread of the disease in sheep in Sharkia province. Thus further studies will be needed to clarify the role of sheep in epidemiology of infection and transmission to other susceptible animals.(2) All vaccinated sheep with bivalent AL (OH)3 gel exhibited specific antibodies after 3 and 4 WPV by ELISA and SNT respectively.(3) Specific FMD antibodies were detected by ELISA and SNT after 2 & 3 WPV in sheep vaccinated with oil adjuvant Montanide ISA 206 bivalent (O1 and A/Egypt 2006) FMD vaccine.(4)There were a correlation between the results of SNT and ELISA, even though ELISA can detect immune response against FMD earlier than SNT.(5)Vaccination of sheep with inactivated oil adjuvant Montanide ISA 206 vaccine gave higher long lasting immunity than AL (OH)3, so can lead to decrease the number of revaccination times.