Four groups of one-day-old SPF chicks were inoculated with the four IBV variants at 1 day old to study the virulence of these isolates. The results at 2 weeks post infection (PI) revealed that all isolates were able to induce serological resposne postinfection, respiratory distress and depression. 20% and 100% mortalities were recorded with isolates 4 and 23; respectively. Assessment of pathogenicity index and pathotyping (at the end of observation period “2wk-PI"), categorized the 4 tested isoaltes (4, 16,18, 23) into three isoaltes of high virulence (4, 18 and 23), and one isolate of intermediate virulence (16). About 50% reduction in body weight was recorded with the four IBV isolates 2 wk PI. Kidney lesions were nephritis-nephrosis with urate deposition in ureters, while microscopic lesions were associated with increase in the amount of rough endoplasmic reticulum (RER). Tracheal lesions recorded as increase the amount of mucin, while microscopic lesions were edema of mucosa and inflammatory cells in the lamina propria. The regime of administering the infectious bronchitis (IB) live commercial H120 vaccine at 1 day old SPF chicks, and the heterologous challenge with four variants (serotypes) at 4 weeks of age, was found to be poorly effective in protecting the respiratory tract of SPF chickens with protection percentages of 8.1%, 55%, 10.5% and 12.6% corresponding to field isolates of IBV 4, 16, 18 and 23; respectively. Protection was measured by assessing ciliary activity of the tracheal epithelium following challenge. It is suggested that the use of the live IB-H120 vaccine will not always broaden the protection against challenge with IB multiple serotypes isolated from Egypt. Therefore it is necessary to develop a new IB vaccines, either locally prepared or imported to overcome any new IB serotype that were emerged, through modifying vaccination strategies to make them appropriate to the field situation.