The responses of vaccinated and unvaccinated chickens of different breeds to infection with very virulent infectious bursal disease virus (vvIBDV) were investigated. Five-week-old chickens of five Egyptian breeds (Fayoumi, Balady, Golden, Mandarah, and Gimmizah), and foreign White Leghorn pullets were tested. In unvaccinated birds, mortality, relative bursa and spleen weight, bursal lesion score, antibody titres and the response of blood lymphocytes to mitogens were examined. The Gimmizah and Fayoumi birds showed the greatest susceptibility to infection with mortalities of 85 and 47%, respectively. Mandarah birds were resistant (11% mortality), while the Leghorn, Golden and Balady birds were of intermediate susceptibility (20, 21 and 37% mortality rates, respectively). Vaccinated birds were administered a live intermediate classic vaccine and challenged 10 days later with vvIBDV. Mortality following challenge was about 3% in the Fayoumi, Gimmizah and Balady birds, whereas no mortality was seen in Mandarah, Golden, and Leghorn birds. The classic vaccine induced significant protection. However, it did not prevent histological bursal lesions, especially in the Fayoumi and Leghorn birds. Neither pathological nor immunological measures correlated closely with susceptibility or resistance of the different breeds. The findings suggest that innate non-immunogenic factor(s) may play a critical role in resistance.