The expression of Ia-like (class II MHC) antigens on canine hemopoietic cells was investigated using a cytotoxic murine monoclonal antibody, WM-2, reactive with dog Ia-like antigens. Another monoclonal antibody, WMD-1, reactive with canine Thy-1 antigen, was used as a positive control. Depletion of Ia+ cells from dog bone marrow by complement-mediated lysis with WM-2 antibody failed to inhibit growth of granulocyte-macrophage progenitors (CFUgm) in vitro, while WSMD-1 produced complete inhibition of CFUgm. Lethally irradiated dogs receiving bone marrow autografts depleted of Ia positive cells ex vivo showed initial engraftment, followed by prolonged pancytopenia, and eventual complete recovery of marrow function in the majority of animals. In contrast, dogs receiving autografts treated with WMD-1 and complement all died of marrow failure. We interpret these results as indicating: (1) that Thy-1 antigen is present on hemopoietic stem cells essential for marrow engraftment; (2) that the expression of Ia antigens on hemopoietic stem cells essential for marrow engraftment; and (2) that the expression of Ia antigens on hemopoietic cells is heterogeneous and related to the level of stem cell maturation. While Ia appear to be present on a stem ell population at an earlier stage than CFUgm, as evidenced by the transient phase of graft failure seen in dogs receiving Ia-depleted marrow, the most primitive stem cell, responsible for long -term engraftment, is effectively Ia-negative.