Homologous interference in vitro is defined as the ability of primary viral infection to prevent secondary homologous superinfection. Non-cytopathic bovine viral diarrhea virus (ncp BVDV) has been classified according to the exaltation of Newcastle disease phenomenon (END) as END positive (E+) and END negative (E-) strains. Simultaneous inoculation of MDBK-SY cell monolayers with BVDV/E- virus and a three log higher amount of BVDV RK13/E+ virus, leads to acquisition of the BVDV/E- feature of blocking Newcastle disease virus (NDV) infection in cells. BVDV/E- strains, particularly at a high titre and MOI ≥1.25, can exert and impose their effects in BVDV/E+ infected cells; however, if BVDV/E- MOI is reduced to MOI below 0.625, the BVDV/E+ effect can be restored leading to cytopathic effects (CPE) induction by NDV reciprocal to the titre of the BVDV RK13/E+ strain. Moreover, blocking and prevention of induced CPE by NDV or vesicular stomatitis virus (VSV) occurs even when BVDV/E- superinfects primary BVDV/E+ infected cells, indicating a defective homologous interference between BVDV/E+ and BVDV/E- strains. Taken together, BVDV/E- strains have a strong competitive potency and mediate a fast acting (i.e. within 60 min) influence against BVDV/E+ activity. This may be relevant in vivo where BVDV/E- and BVDV/E+ combinations are frequently isolated from infected individuals.