The pathogenesis of bluetongue infection was studied by the titration of the virus in tissue samples taken from sheep inoculated subcutaneously in the auricula of the ear with 76 TC ID₅₀ the plaque-purified type 10 bluetongue virus. Tissue samples were taken from individual animals killed at daily intervals over a period of 11 days. The mean incubation time was 6, 9 days and the first clinical sign was pyrexia. On the 4th day, bluetongue virus was demonstrated in the lymph nodes of the cephalic area, tonsils and spleen; viraemia became demonstrable on the 6th day post-inoculation and typical macroscopic lesions due to the virus were first observed on the 8th day. It was concluded that, post-infection, the virus entered the regional lymph nodes. From there it was disseminated via the lymph and/or the blood stream to the lymphoid tissues in other parts of the body where further replication occurred. From these primary sites the virus was carried via the blood stream and infected the majority of tissues. Humoral antibody, as detected by immunofluorescence, did not appear to have a direct influence on the concentration of virus in solid tissues. Persistence of the virus in infected sheep was not demonstrated when tissues were taken 6, 8 and 16 weeks after infection.