An established mouse model was used to evaluate the effectiveness of the major outer core protein of African horsesickness virus (AHSV), VP7, as a subunit vaccine. Adult female BALB/c mice were immunized with VP7 crystals purified from BHK cells infected with AHSV serotype 9 (AHSV-9), using three inoculations in Freund's adjuvant. Eighty to one hundred per cent of the immunized mice were protected against a heterologous challenge with a known lethal dose of AHSV-7. The protected immunized mice did not develop any clinical signs characteristic of virulent AHSV infection in this model during the study. In contrast, 80-100% mortality was observed in the non-immunized mice that received the same challenge virus. Subsequent studies indicated that a single inoculation of 1.5 micrograms purified AHSV VP7 in Freund's complete adjuvant was sufficient to protect at least 90% of mice from AHSV-7 challenge. If the antigen was presented in the absence of Freund's complete adjuvant, 70% of the mice were still protected by one inoculation of VP7 crystals. Titres of circulating antibody against AHSV VP7, determined by competitive ELISA, did not appear to correlate with protection and passive antibody transfer from immunized BALB/c mice failed to protect syngeneic recipients from AHSV-7 challenge. Therefore, the observed protection is unlikely to be due to an antibody-mediated immune response. The number of viraemic mice and the duration of viraemia post-challenge was significantly reduced in vaccinated mice compared to non-vaccinated controls. However, the levels of viraemia were similar.