Technical Abstract: Members of the receptor-like kinase gene family play crucial regulatory roles in many aspects of plant development, but the ligands to which they bind are largely unknown. In Arabidopsis, the receptor kinase CLAVATA1 (CLV1) binds to the small secreted polypeptide CLV3, and three proteins act as key elements of a signal transduction pathway that regulates shoot apical meristem maintenance. To better understand the signal transduction mechanisms involving small polypeptides, we are studying 25 Arabidopsis CLV3/ESR (CLE) proteins that share a conserved C-terminal domain with CLV3 and three maize ESR proteins. Members of the CLE gene family were identified in database searches and only a few are known to be expressed. We have identified an additional member of the CLE gene family in Arabidopsis, which is more similar in gene structure to CLV3 than the other CLE genes. Phylogenetic analysis reveals that few of the putative CLE gene products are closely related, suggesting there may be little functional overlap between them. We show that 24 of the 25 Arabidopsis CLE genes are transcribed in one or more tissues during development, indicating that they do encode functional products. Many are widely expressed, but others are restricted to one or a few tissue types. We have also determined the sub-cellular localization of several CLE proteins, and find they are exported to the plasma membrane or extracellular space. Our results suggest that the Arabidopsis CLE proteins, like CLV3, may function as secreted signaling molecules that act in diverse pathways during growth and development.