Two techniques performed on skin biopsy samples (ear notches), immunohistochemistry (IHC) and antigen-capture ELISA (AgELISA), were compared for detection of bovine viral diarrhea virus (BVDV) persistent infection (PI) in 559 Angus calves between the ages of 1 and 5 months. The calves also were tested for BVDV infection using virus isolation (VI) and reverse transcription (RT)-PCR on buffy coat samples and for antibodies to BVDV types la and 2 by serum neutralization (SN). Sixty-seven of 559 (12.0%) calves tested positive at initial screening by IHC, AgELISA, or VI, and all 67 were kept for a minimum of 3 months and retested monthly by IHC, AgELISA, VI, RT-PCR, and SN. Of the calves positive at initial screening, 59/67 (88.1%) were determined PI and 8/67 (11.9%) were determined acutely infected. Both IHC and AgELISA detected 100% of PI calves; however, IHC and AgELISA also detected 6 and 8 acutely infected calves, respectively, at initial screening. Furthermore, IHC and AgELISA continued to detect 3 and 4 acutely infected calves, respectively, 3 months after initial screening. Three acutely infected calves had IHC staining indistinguishable from PI calves at initial screening. Both IHC and AgELISA are accurate at detecting BVDV-infected calves, but veterinarians and producers should be advised that both tests detect some calves acutely infected with BVDV in addition to PI animals. Repeat testing using VI or RT-PCR on buffy coat samples should be performed at 30 days after initial screening to conclusively discriminate between acute and PI.