The purpose of this study was to investigate the influence of the cytostatic drug, 5-fluorouracil (5-FU), which causes depletion of heterophil granulocytes, on clinical symptoms and histological lesions during the progress of infectious bursal disease virus ( IBDV) infection in chickens. The aim was to disclose the mechanism behind the clinical disease symptoms. Three groups of specific pathogen free chickens were used for the experiment. Chickens in groups 1 and 3 were pretreated with 5-FU, while chickens in group 2 were treated with a placebo. After 5 days, the chickens in groups 2 and 3 were inoculated with the classical IBDV strain F52/70. Bursae of Fabricius were sampled at fixed intervals, and the progress of the infection was monitored by various histological techniques and reverse transcriptase-polymerase chain reaction (RT-PCR). We found correlation between histological observations and RT-PCR results. In the 5-FU pretreated chickens, IBDV caused only mild clinical symptoms, even though histological alterations similar to alterations caused by IBDV were still observed. The 5-FU pretreatment resulted in severe heterophil granulocyte depletion by days 2 and 3 after infection (post inoculation) and increased numbers of bursal secretory dendritic cells in the medulla of the follicles. IBDV infection seemed to induce fusion of secretory dendritic cells, resulting in formation of multinucleated giant cells, loaded with apoptotic B cells and virus particles associated with granules of bursal secretory dendritic cells. Our results indicate that the heterophil granulocytes together with the bursal secretory dendritic cells contribute to the outbreak and/or progress of clinical symptoms.