The reticulon (RTN) family of proteins has been described as a new eukaryotic protein family. We have isolated Xenopus cDNA homologues of RTN2 and RTN3 and examined their expression patterns during Xenopus development. XRTN2 has two transcripts, XRTN2-B and XRTN2-C, which encode 321 and 191 amino acids, respectively. XRTN3 has only one transcript that encodes 214 amino acids. We detected the XRTN2-B transcript in the neural tissues and brain from the early neurula stage. XRTN2-C is strongly expressed in the myotome, future skeletal muscle. The XRTN3 mRNA is localized in the animal hemisphere of the egg and blastula stage embryos and then subsequently restricted, mainly in the neural tissues. At the subcellular level, The XRTN proteins are expressed in the endoplasmic reticulum network structure of the animal cap cells as well as COS-7 cells. Our results suggest the potential roles of XRTN2s and XRTN3 during Xenopus embryogenesis. Developmental Dynamics 233:240–247, 2005. © 2005 Wiley-Liss, Inc.