Insect cells co-infected with appropriate recombinant baculoviruses synthesize double-shelled virus-like particles (VLPs) with bluetongue virus (BTV) VP2 proteins representing serotype 1 (BTV-1), 2 (BTV-2), 10 (BTV-10), 13 (BTV-13) or 17 (BTV-17) as previously reported for BTV-10 (French, T.J., Marshall, J.J.A. and Roy, P. J. Virol, 1990, 64, 5696-5700). The derived particles were purified and used to vaccinate sheep, either as single VLP types (BTV-10, BTV-17) or as a combination of all five serotypes. Control sheep received saline. The virus-neutralizing antibody responses were measured. Depending on the experiment, the sheep were challenged with homologous (BTY-10, -13, -17) or selected heterologous (BTV-4, -11, -16) viruses either after 4 months or 14 months, and the disease, viraemias and clinical reactions monitored. The results indicated that two doses of 10 mu g of VLPs elicited a long-lasting immune response which protected the sheep against challenge with the homologous virulent virus. In certain cases, partial protection was afforded against challenge by heterologous BTV serotypes.