Aims To evaluate the in vitro and in vivo effectiveness of egg yolk immunoglobulin (IgY) against periodontal disease-causing Fusobacterium nucleatum. Methods and Results Four White Leghorn hens (120days old) were immunized with whole Fusnucleatum cells killed with 1% formaldehyde using three injections provided at 2-week intervals. IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. This IgY was shown to have a purity of 86.8% based on its optical intensity in the stained SDS-PAGE bands. An enzyme-linked immunosorbent assay indicated a high specificity for the IgY against Fus.nucleatum with a maximum antibody titre of 80 000. The IgY had only weak cross-reactivity with Porphyromonas gingivalis, Prevotella intermedia and Solobacterium moorei. Growth and biofilm formation by Fusnucleatum were inhibited by IgY at concentrations of 10 and 20mgml-1. Immunofluorescence and immunoelectron microscope assays revealed a high binding ability of specific IgY, which may explain the in vitro effectiveness of IgY. In an in vivo study, IgY treatment resulted in a marked decrease in alveolar bone loss after Fusnucleatum infection in a mouse model confirming the effectiveness of IgY against periodontal disease-causing Fus similar to nucleatum. Conclusions IgY effectively inhibited growth and biofilm formation by Fus similar to nucleatum and prevented the progression of periodontal disease by decreasing alveolar bone loss. Significance and Impact of the Study Specific IgY may have potential for the treatment of periodontal disease.