Newcastle disease virus is a major threat to poultry and in ovo vaccines are needed. A live in ovo vaccine for Newcastle disease virus, which was licensed but not marketed, was unsafe. It killed 32% of line 0 chicks and 10% of vaccine Lohmann (VALO) chicks using the maximum recommended dose that infected about 40% of the embryos. VALO's made more antibody than line 0's whether infected in ovo or by contact. The vaccine interrupted the massive development of the air capillaries between injection and hatch 3 days later. Cytokines, delivered as DNA in plasmids, did not function as adjuvants. IFN-gamma prevented infection. IL-4 or IL-18 had little or no effect. Line 0 chicks that had been infected by contact were protected and so the unsafe in ovo vaccination of a minority could protect the majority.