A number of cDNAs encoding mutant forms of the murine haemopoietic growth factor, granulocyte/macrophage-colony-stimulating factor (GM-CSF), have been derived by in vitro mutagenesis and expressed in simian COS cells. Determination of the biological activity of the mutant factors revealed that residues within the regions 11-15, 24-37, 47-49 and 81-89 are required for generating a functional GM-CSF molecule. In particular, truncation of either of two strongly predicted alpha helices near the N terminus of the molecule severely depresses the activity of the factor.