We have recently reported that cattle and pigs which have been vaccinated against foot-and-mouth disease can be distinguished from convalescent animals by the absence of antibodies to viral non-structural protein 2C (Lubroth and Brown, Res. Vet. Sci., 1995, 59, 70-78(1)). In this study, we show that the absence of 2C antibodies from the sera of vaccinated animals can be explained by the association of this viral protein with cellular debris which is separated from the virus harvest prior to inactivation of the supernatant for vaccine production. This serological marker can be of great value in countries where the disease occurs or in the veterinary regulatory arena when livestock are transported across borders, since it can be used to identify convalescent, persistently infected animals and vaccinates exposed to wild-type virus variants which have infected the vaccinated animals.