The properties of clonogenic and leukemic cells, derived from mice infected with different helper virus pseudotypes of the polycythemic strain of Friend spleen focusforming virus (SFFV p), have been analyzed. Four different replication-competent murine leukemia viruses (MuLVs) were used as helpers for the defective SFFV, genome: the Friend MuLVs, Moloney MuLV, and an amphotropic MuLV. Three different biological parameters were measured: (i) the kinetics of emergence of clonogenic cells characteristic of the late stages of Friend erythroleukemia; (ii) the ability of cells in these colonies to give rise to secondary colonies (self-renewal capacity); and (iii) the capacity of cell lines derived from these colonies to respond to inducers of erythroid differentiation. The properties of these cells was found to be independent of the helper virus used, suggesting that it is the SFFV, genome, not the helper virus, that plays a determinant role in the late stages of erythroleukemia.