The progress and pathogenesis of foot-and-mouth disease virus (FMDV) was studied in infected pigs by observing the development of clinical signs in two separate experiments. Viral loads were determined by real-time quantitative RT-PCR in the liver, spleen, cervical lymph node, mandibular lymph node, retropharyngeal lymph node, soft palate, pharynx, tonsil, tongue and skin (coronary band area). Tissue samples were collected from both inoculated and contact-infected pigs at several time points during infection, and blood samples were collected to assess viraemia and its relationship to tissue viral load. Virus first appeared in the lymph nodes, followed by viraemia and then clinical signs. The results suggested that FMDV accumulated in lymphoid tissue up to six hours after infection, in the tissues drained by the mandibular lymph node and tonsil and then disseminated throughout the body where epithelial cells were the favoured sites of replication.