Specific-pathogen-free chickens immunized at 14 days of age with either an inactivated recombinant Newcastle disease virus–LaSota/avian influenza H5 (K-rNDV-LS/AI-H5) vaccine or a killed Newcastle disease/avian influenza whole-virus vaccine (K-ND/AI) were protected from disease when challenged with either A/chicken/Queretaro/14588-19/95 (H5N2), a high pathogenicity avian influenza virus (HPAIV) strain isolated in Mexico in 1995, or with a Mexican velogenic viscerotropic Newcastle disease virus (VVNDV) strain 21 days postvaccination. All nonvaccinated chickens challenged with HPAIV or VVNDV succumbed to disease, while those vaccinated with K-rNDV-LS/AI-H5 or K-ND/AI were protected from severe clinical signs and death. Both vaccines induced hemagglutination-inhibition (HI) antibody responses against NDV and AIV. Antibodies against AIV nucleoprotein were not detected by enzyme-linked immunosorbent assay (ELISA) in birds vaccinated with the inactivated rNDV-LS/AI-H5 vaccine. These chickens became positive for AIV antibodies by ELISA only after challenge with HPAIV. The data clearly indicate that the inactivated rNDV-LS/AI-H5 vaccine confers protection comparable to that of the conventional killed whole-virus vaccine against both NDV and AIV, while still allowing differentiation of infected from vaccinated animals by HI and ELISA tests.