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For transplantation of semiallogeneic bursal stem cells into cyclophosphamide-treated 3-day old chicks, two lines of chickens homozygous at the major histocompatibility locus and their F(1) hybrids were used in reciprocal combinations. The semiallogeneic transplantations resulted in a complete restoration of antibody formation to sheep red blood cells (SRBC) and Brucella, of microscopic morphology of bursa fabricii, and of germinal center formation in the spleen. In contrast, allogeneic bursal stem cells were not effective in restoring secondary response to SRBC and germinal center formation, while they were able to reconstitute anti-Brucella responses and bursal morphology. These findings indicate an effective cooperation of donor and host cells leading to a complete restoration of the bursa-dependent lymphoid system, when the donor and recipient share at least one haplotype determining the major histocompatibility antigen complex.