The primary aim of a bovine virus diarrhea virus (BVDV) vaccine is to prevent transplacental transmission of virus. We studied the efficacy of two experimental conventionally inactivated vaccines, based on BVDV strain Singer and containing a different antigen amount, against three antigenically different BVDV strains in a vaccination-challenge experiment in sheep. We also studied the efficacy of an experimental multivalent E2 subunit vaccine against four antigenically different BVDV strains. The vaccine contained the glycoproteins E2 of BVDV strains that belong to antigenic groups IA, IB and II. All three vaccines induced neutralizing antibodies against all challenge strains. Only the conventional vaccine that contained the highest antigen amount induced complete protection against homologous challenge. Neither of the conventional vaccines provided complete protection against heterologous challenge. The multivalent subunit vaccine induced partial protection against the homologous challenge strains. However, the immune response did inhibit virus replication in ewes, as shown by the results of the virus titrations.