Ten gnotobiotic lambs and 4 gnotobiotic kids inoculated with virulent bluetongue virus (BTV) including BTV international types 10, 11, 13, and 17 did not show clinical signs of bluetongue. Seroconversion was observed in all gnotobiotes and conventional control sheep inoculated with the appropriate challenge BTV. Viremia was detected in 1 BTV-infected gnotobiote. Conventional control sheep inoculated with a given BTV international serotype showed a marked febrile response with hyperemia of the nasal and buccal mucosa.