Cyclophosphamide-treated 4-day-old chicks were injected with cells from yolk sac, liver, bursa of Fabricius, bone marrow, spleen and thymus by using embryonic and 4-day-old donors. Recipients and donors were isogeneic at the major histocompatibility locus. Survival pattern, gain of body weight, production of natural and immune antibodies, and microscopic morphology of bursa and spleen were studied to assess the reconstitution achieved. Of all the cell types used, only bursa cells were capable of a functional and morphologic reconstitution of the bursa-dependent lymphoid system. These findings are interpreted to indicate that in embryonic life and immediately after hatching the bursa alone possesses cells that can home to the bursa of 4-day-old chicks and re-establish its functions. These cells derived from embryonic liver and yolk sac are considered stem cells for humoral immunity. The findings illustrate the significance of the critical developmental relationship between the stem cell and its environment.