Neutralizing monoclonal antibodies raised against intact foot-and-mouth disease virus type O1 reacted with intact virus and trypsin-treated virus particles. Some of the monoclonal antibodies showed a slight but definite reaction with the 12S subunit, but none of them reacted with the isolated capsid protein VP1 or any of the other viral proteins. These results confirm the difference between the neutralizing antigenic determinants exposed on intact virus particle and on isolated capsid protein VP1. They suggest further that the neutralizing antigenic determinant and the cell attachment site are not identical.