An efficient induction of wasting disease in chickens by avian leukosis virus (ALV), particularly ALV subgroup C, requires >102 infectious units virus inoculated in mid embryogenesis. The most conspicuous symptoms of the disease were induced by ALV subgroup C; however, significant differences in the occurrence of wasting disease were found among individual members of this subgroup. Almost comparable pathogenicity was exhibited by ALV subgroup D, whereas viruses of subgroups B and A proved to be moderately and almost non-pathogenic, respectively. Using antibodies to cellular antigens, tissue alterations were shown clearly in ALV-C-infected chickens. An essential feature was depletion of lymphocytes in the thymus, bursa and spleen. While the number of dendritic cells in the bursa was increased, their representation in the thymus and spleen was reduced. In the spleen, however, the reduction of dendritic cells concerned only an ellipsoid compartment, which in itself was also markedly reduced. An increased number of macrophages in the thymus and spleen corresponded with the observed general activation of the monocyte-macrophage system. In the spleen, CD4+ T cells were reduced while CD8+ T cells were increased. In agreement with this finding was a failure of chickens to respond to Brucella antigen and an inability of their splenocytes to respond to Concanavalin A, both of which pointed to the damage of immune reactivity. Variation in the pathogenicity among individual ALV strains provides ground for depicting gene sequences playing an important role in ALV acute pathogenicity.