In a series of experiments, the envelope glycoprotein (G protein) of bovine ephemeral fever virus (BEFV) induced immunity against challenge with virulent virus. Protection correlated with the level of specific serum antibodies to G protein measured by a blocking ELISA test and with the level of neutralizing antibody. The optimum vaccination regimen consisted of two injections given 21 days apart at a dose rate of 0.32 microgram per cow of purified G protein emulsified in the adjuvant Quil A. This schedule conferred immunity for the duration of the preliminary experiment (46 days). Immunity to severe disease, but not to infection, remained for at least 12 months after vaccination, although BEFV could not be reisolated from vaccinated cattle following challenge. Unvaccinated cattle used as controls exhibited typical signs of clinical ephemeral fever and BEFV was recovered from all control animals following challenge.