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 Giα proteins. Out of 8 synthetic peptides with sequence variations of HP5b, those with the closest similarity to the Giα sequence are biologically active. The inhibitory effect appears to be dependent on the blocked N‐tenninus. It is postulated that these peptides may interfere with signal transduction mediated by Gα proteins.