The aim of this study was to evaluate the ability of a pentavalent (BVDV types 1 and 2, BHV-1, BRSV, and PI-3) modified live virus (MLV) vaccine given to 1-2-, 4-5-, and 7-8-week-old calves with maternal antibodies to induce humoral and cellular immune responses and protect calves from virulent BVDV type 2. Eight calves in each age group were vaccinated and four served as controls. All calves were challenged intranasally with BVDV type 2, 12 weeks after vaccination. SVN titers to all five viruses declined in all groups after vaccination (except 4-5-week-old calves to BVDV type 1). After challenge, the SVN titers for both types of BVDV showed anamnestic responses in calves vaccinated at 4-5 and 7-8 weeks, but not at 1-2 weeks of age. In all groups, T cell subsets responded specifically to BVDV types 1 and 2 but not to BHV-1, BRSV, or PI-3 after vaccination by increasing their expression of activation markers (CD25, IFN-gamma and IL-4). All vaccinated calves were significantly protected from BVDV type 2 challenge.