The Gab2^−/− microenvironment is not defective in support of cells capable of multilineage hematopoietic repopulation. To determine whether a component of the defects observed from donor Gab2^−/− BM could be due to cell-extrinsic defects in the microenvironment, we used a BM chimera approach. Wild-type CD45.1 BM cells were transplanted into lethally irradiated wild-type or Gab2^−/− (CD45.2) recipients. A similar transplantation was performed with wild-type CD45.2 BM into CD45.1 recipients. Eight weeks after transplantation, the hematopoiesis was greater than 95% donor derived as indicated on the upper two graphs; the mice were killed, and the BM grafts were competed against each other (CD45.2 vs CD45.1). Shown in the lower graph are analyses of engraftment obtained 8, 12, and 16 weeks after secondary transplantation. No significant difference was observed when either wild-type or Gab2^−/− mice were used as primary hosts (P < .1). Error bars represent the average plus or minus a standard deviation.