Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a potent stem cell inhibitor and a member of a large and expanding family of related cytokines. In an effort to understand the molecular basis of the activities of MIP-1 alpha, we have sought to characterize the cellular receptors for this molecule. Our results demonstrate the presence of abundant MIP-1 alpha receptors on both human and murine cells. The receptor on K562 cells can bind a range of members of the MIP-1 alpha family and may thus be a general MIP-1 alpha family receptor. Murine FDCPmix cells also bind a range of members of this peptide family, although the receptor(s) that they express appear somewhat more selective for peptides capable of displaying stem cell inhibitory properties. The human and murine receptors do not bind members of the related interleukin 8 family of peptides and are thus distinct from the recently cloned interleukin 8 receptor. We suggest that the receptor on the murine cell is a candidate for the receptor responsible for articulating stem cell inhibitory signals following MIP-1 alpha binding.