Crossbred beef calves (n=253) from three breeding herds were used to determine the effects on health, performance, and immune response of different pentavalent (bovine herpesvirus-1, bovine viral diarrhea virus (BVDV) types 1 and 2, parainfluenza-3 virus, and bovine respiratory syncytial virus) modified-live virus (MLV) vaccine regimens administered initially at either 62 or 188 days of age. Calves were stratified by date of birth, gender, body weight and dam parity, then assigned randomly to one of two vaccine regimens. The early vaccination (EV) treatment group was administered a pentavalent MLV respiratory vaccine containing Mannheimia haemolytica leukotoxoid on day 0 (average calf age=62ñ17 days). The traditional vaccination treatment (TV) group received the same respiratory vaccine on day 126 (average calf age=188ñ17 days). Both treatment groups were revaccinated with the MLV respiratory vaccine on day 147 (weaning). A clostridial bacterin-toxoid was administered to all calves on days 0, 126, and 147. A subset of mixed-gender calves (n=52/treatment) and steers (n=10/treatment) were randomly selected to provide blood samples for measurement of the humoral and cell-mediated immune assays, respectively. To determine humoral immune response, blood was collected on days 0, 21, 126, 147 (weaning), 175, and 231, and serum was harvested for later determination of BVDV type la (Singer strain) serum neutralization antibody titers. Peripheral blood mononuclear cells were harvested from anticoagulated blood collected on days 0, 7, 21, 42, 126, and 189 to conduct cell population analysis indicative of CD25 expression index using a multi-parameter flow cytometry assay. No calves required treatment for bovine respiratory disease during the study, which ended after an 84-day post-weaning period. Interim and overall gain performance were similar (P?0.84) between vaccine treatments throughout the study. On day 0, serum BVDV type la antibody titers were present, presumably from passive BVDV antibody transfer via colostrum, but did not differ (P=0.50) between vaccine treatments. However, BVDV antibody titers were greater for EV calves compared to TV calves on days 21, 126, and 147. There was a treatment ? day interaction (P=0.05) for the CD25 expression index of CD8+ cells; EV calves had a greater expression index than TV calves on day 126. Differences in BVDV type la titer concentrations and CD25 expression indices observed in this study suggest that calves develop both humoral and cell-mediated immunity when vaccinated at 62 days of age. Furthermore, growth performance or health was not affected by vaccine regimen, which supports early vaccination as a cost-effective alternative to traditional calfhood vaccine regimens.