Previous work has shown that part of the hierarchical structure of the hematopoietic system can be described by HPP-CFC-1 (primitive high proliferative potential colony-forming cells responding to colony-stimulating factor-1 [CSF-1] + interleukin-3 [IL-3] + IL-1), HPP-CFC-2 (more mature HPP-CFC responding to CSF-1 + IL-3), and mature HPP-CFC responding to the single factors, CSF-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-3. In this study, we have attempted to relate the murine HPP-CFC, stimulated by various combinations of growth factors (GFs)--CSF-1, GM-CSF, IL-3, IL-6, IL-1, stem cell factor (SCF), and transforming growth factor-beta (TGF-beta)--and by CSF-1, GM-CSF, and IL-3 on their own, to these known progenitors. Studies involving regeneration of the bone marrow after 5-fluorouracil (5-FU) treatment, generation of progenitors in liquid cultures in response to different GF combinations, and the HPP-CFC content of lineage-negative rhodamine-sorted bone marrow (BM) fractions have indicated that: 1. the combinations CSF-1 + IL-3 + IL-1 + SCF and CSF-1 + IL-3 + IL-1 + IL-6, and possibly CSF-1 + GM-CSF + IL-3 + IL-1, stimulate pre-HPP-CFC-1; 2. the combinations CSF-1 + IL-1 + GM-CSF, CSF-1 + IL-1 + IL-6, CSF-1 + IL-1 + SCF, CSF-1 + IL-3 + SCF, CSF-1 + IL-6 + SCF, and IL-3 + SCF, appear to overlap with the CSF-1 + IL-3 + IL-1 combination to stimulate the more mature cells of the HPP-CFC-1 compartment; 3. the combinations CSF-1 + GM-CSF, CSF-1 + IL-1, CSF-1 + IL-6, and CSF-1 + SCF may stimulate the more mature cells of the HPP-CFC-2 population, while the single factors CSF-1, GM-CSF, and IL-3, as suggested in other reports, may stimulate HPP-CFC that are more mature than the HPP-CFC-2; 4. the combinations IL-3 + IL-6 and SCF + IL-6 appear to stimulate HPP-CFC that overlap with the HPP-CFC-1 population, while those responding to the combination GM-CSF + TGF-beta overlap with the HPP-CFC-2 population within the hematopoietic hierarchy; and 5. CSF-1 and GM-CSF appear to be interchangeable in the combinations studied.