The objectives of this study were to evaluate the role of cellular and humoral immune response to Newcastle disease virus (NDV) in relation to protection. Two different strategies were used to investigate the role of cell mediated immunity (CMI) in protection of birds from NDV. In the first strategy, 3-week-old birds were vaccinated with either live (LNDV), inactivated (UVNDV), SDS treated NDV or phosphate buffered saline (PBS). The birds were boostered at 5 weeks and challenged at 6 weeks. Only those birds that had specific CMI and a specific antibody response were protected, whereas birds with demonstrable CMI but no specific antibody response were not protected;In the second strategy, birds from SPF embryos were treated in ovo with cyclophosphamide (CY) to deplete B cells. At 3 weeks of age birds were vaccinated with either LNDV, UVNDV or PBS along with CY-untreated control birds. The birds were boostered at 5 weeks and challenged at 6 weeks. Only those birds that had specific CMI and antibody responses to LNDV or UVNDV were protected. Both strategies indicated the presence of specific antibodies is important in providing protection from Newcastle disease;The role of humoral immune response in protection of birds from ND was investigated. Birds were passively immunized with hyperimmune sera directed against individual NDV polypeptides or whole virus. Only those birds that were passively immunized with antisera directed against surface glycoproteins (HN and F) and whole virus were protected whereas chickens passively immunized with antisera against internal proteins (NP/P and M) developed clinical signs of ND and died. The challenge virus was recovered from all passively immunized groups. It was concluded that the presence of neutralizing antibodies to NDV provided protection from clinical disease but was unable to prevent virus shedding;A technique for inducing B-cell ablation in chickens by in ovo cyclophosphamide injection was developed. In addition, the quantification of neutralizing antibodies to NDV to NDV in the ST cell line was evaluated using a colorimetric 96-well plate microassay. Data from this study support the importance of antibodies as a key component in protection against Newcastle disease.