Currently available data indicate that the earliest identifiable hemopoietic progenitor in normal marrow is CD34+ MHC class II-; subsequent expression of MHC class II antigens is maturation and lineage dependent. Studies on embryonal cells suggest that CD34+DR- cells are actually the common precursors for stromal and hemopoietic elements, with the earliest hemopoietic precursor being CD34+DR+. DQ antigens are apparently not expressed in cells of hemopoietic potential and the expression of DQ appears to be regulated differentially from DR and DP. MHC class II antigens are also expressed on some stromal cells, especially those with endothelial and macrophage features. MHC class II molecules are involved in hemopoietic cell/stroma interaction. The presence of anti-MHC class II monoclonal antibodies (MABs) at early stages of stem cell proliferation/differentiation, at least under conditions of marrow stress, induces signals which may result in final, especially granulocytic, differentiation of later precursors. These may interfere with the survival of those cells which are required for long-term hemopoietic reconstitution. Observations in allogeneic marrow transplant recipients support a role of MHC molecules as expected in allogeneic interactions. Results in autologous models point towards a role of MHC class II molecules other than that of a histocompatibility marker insofar as these molecules or signals transmitted by them appear to be involved in the regulation of hemopoiesis.