Chicken anaemia virus (CAV) is the most important confounding pathogen in Marek's disease virus (MDV) infection. The effect of CAV co-infection at 4 weeks of age after inoculation of virulent MDV (vMDV, KS strain) or very virulent MDV (vvMDV, Md/5 strain) in 1-day-old chicks was investigated by pathological and immunohistochemical studies. CAV increased the mortality rates induced by vMDV or vvMDV. The packed cell volume was reduced significantly in vMDV-CAV infection; however, no reduction or non-significant reduction was observed in vMDV infection. Bone marrow hypoplasia was related to CAV co-infection and none of the birds inoculated with vMDV or vvMDV had hypoplasia. Severe atrophy of the thymus and bursa of Fabricius was observed in the vvMDV-CAV and vvMDV groups. Complete regeneration of the thymus cortex and bursa of Fabricius in the vMDV group was noted and was in contrast to sequential lymphoid depletion after CAV inoculation in the vMDV-CAV group. The spleen was either regenerated, lymphoid depleted or had lymphoproliferative lesions. Lymphoid depletion in the spleen was not detected in the vMDV group; however, it was prominent in the vMDV-CAV and vvMDV-CAV groups during the first 2 weeks after CAV inoculation. CAV inclusions and antigens were detected in the thymus cortex and spleen of vMDV-CAV and vvMDV-CAV groups during the experiment. Severe depletion of CD8(+) T cells was observed in depleted spleen and thymus. The neoplastic foci appeared around splenic arterioles and venules, and stained mainly by CD4 antibody; however, CD8(+) T cells were singly dispersed or were present in clusters. It could be concluded that CAV was responsible for bone marrow hypoplasia, severe anaemia and hindrance of lymphoid organ regeneration in MDV-CAV co-infection.