The hemoregulatory peptide PyroGlu-Glu-Asp-Cys-Lys (HP5b), which inhibits myelopoietic colony formation in vitro, is shown to be a sequence motif which is also part of the effector domain of Gi alpha proteins. Out of 8 synthetic peptides with sequence variations of HP5b, those with the closest similarity to the Gi alpha sequence are biologically active. The inhibitory effect appears to be dependent on the blocked N-terminus. It is postulated that these peptides may interfere with signal transduction mediated by Gi alpha proteins.