Mouse bone marrow cells were exposed to specific monoclonal antibodies, so that lineage positive (Lin+) cells could be removed with magnetic beads. The Lin- cells were cultured with Sca-1 or CD90 (Thy-1) monoclonal antibodies (MoAbs) in semi-solid medium for 7 d. We found that Sca-1 MoAb suppressed colony formation (20-30%), and the effect was largely abolished by N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase. Similar results were obtained with antibodies to CD90. The findings suggest that the unknown physiological ligands to Sca-1 and Thy-1 markers on haematopoietic progenitor cells can inhibit colony formation, with NO as a pivotal mediator. Primitive progenitors may be a primary target of this Sca-1 ligand, as the Sca-1+ cell population contains the major part of the multipotent haematopoietic stem cells.