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In future, a policy of "vaccinate-to-live" may be included in the repertoire of foot-and-mouth disease (FMD) control measures and in support of this approach, we have investigated the hypothesis that vaccine-induced reduction in virus replication and excretion from pigs can be correlated to the severity of clinical signs of FMD by measuring excretion of virus in natural secretions and aerosols. The other aims of this study were to verify the existence of sub-clinical infection in vaccinated pigs, to evaluate the correlation between this and seroconversion to foot-and-mouth disease virus (FMDV) non-structural protein antibodies and to re-examine the occurrence of FMDV persistence in the oro-pharynx of pigs. Therefore, pigs were vaccinated (O1 Manisa) and challenged (O1 UKG) in a manner calculated to produce a broad range of clinical outcomes and were monitored for a minimum of another 33 days post-challenge. Eighty-one percent of the early (10 days vaccinated) challenged pigs and 25% of the late (29 days vaccinated) challenged pigs were clinically infected and all other vaccinated pigs were sub-clinically infected. Although vaccination could not provide complete clinical or virological protection, it reduced the severity of the disease, virus excretion and production of non-structural FMDV antibodies in vaccinated and subsequently infected pigs. As hypothesised, vaccine-induced reduction of virus replication and excretion was found to be correlated to the severity of clinical disease. RNA copies, but no live virus was detected from the pharyngeal and soft palate tissues of a minority of vaccinated and infected pigs beyond the acute stage of the infection.