Porcine circovirus-associated disease (PCVAD) is considered a multifactorial disease since a variety of cofactors, including infectious agents, seem to be necessary for full expression of clinical disease. In order to investigate the role of ruminant pestiviruses in PCVAD that has been frequently detected from field cases, two studies were conducted. Porcine circovirus 2-1a (PCV2-1), cytopathic type 1 bovine viral diarrhea virus (cpBVDV) strain NADL and a field strain of BVDV, were inoculated intramuscularly and intranasally into cesarean-derived, colostrum-deprived pigs either alone or in combination in two different experiments. In this study we were able to demonstrate that PCV2 is essential for developing PCVAD clinical signs and disease. Vaccination against BVDV with Aluminum Hydroxide adjuvant in combination of with non pathogenic cpBVDV NADL strain of the virus did not initiated PCV2 virus replication as was observed in a previous study. However, vaccination against BVDV virus lowers the number of infected cells with BVDV and PCV2 virus in the tissues of infected pigs with PCV2-1a inoculums. Results from this study will help veterinarians and producers better understand the role of a newly mutated strain of PCV2 virus during infection in swine. The role of BVDV-like porcine field strains of the virus remains an important issue that needs immediate attention BEFORE this virus change into a more virulent form. It needs to be determined if inoculation with the noncythopatic BVDV strain of the virus adapted to a porcine cell line in combination with PCV2 in different time points or by itself will cause disease. This research area is not well investigated and needs immediate attention.