Duck plague virus, isolated from infected ducks on Long Island, New York, was propagated in duck-embryonic-fibroblast cell culture. Cytopathogenicity and eosinophilic, granular, intranuclear, inclusion bodies were seen in the infected cells. The inclusion bodies appeared as early as 12 hours after virus inoculation and became more pronounced and abundant at 32–36 hours postinoculation with cell culture. Their formation was inhibited by duck plague hyperimmune serum. The first 9 serial passages in cell culture were lethal for duck and duck embryos. In addition, the 5th, 6th, 7th, 8th and 9th passages were lethal for chicken embryos. Each of the 5th and 7th virus passages in duck embryo fibroblasts were further passaged in duck and chicken embryo cell cultures. The resulting viruses were nonvirulent for ducks, elicited the development of a relatively low antibody level, but afforded protection against challenge inoculation with duck plague virus. An anamnestic response in antibody level occurred following challenge inoculation which was equal to the antibody level of ducks surviving experimental infection.