Single copies of an approximately 65-70 residue domain are shown to be present in the sequences of 14 eukaryotic proteins, including yeast byr2, STE11, ste4, and STE50, which are essential participants in sexual differentiation. This domain, named SAM (sterile alpha motif), appears to participate in other developmental processes because it is also present in Drosophila polyhomeotic gene product and related homologues, which are thought to regulate determination of segmental specification in early embryogenesis. Its appearance in byr2 and STE11, which are MEK kinases, and in proteins containing pleckstrain homology, src homology 3, and discs-large homologous region domains, suggests possible participation in signal transduction pathways.