The previous study has shown that repeated D domain-like (Rdd) proteins, a group of novel secretory proteinsconsisting of repeated domains of a cysteine-rich sequence, are involved in the process of blood vessel formation in Xenopusembryo. We performed further experiments to examine the localization of Rdd proteins in embryogenesis. Detection of taggedRdd proteins expressed in blastomeres showed that Rdd proteins formed a high molecular weight complex and existed in theextracellular space. A rabbit antibody against the Rdd synthetic peptide identified a single band of 28 kD in embryonic tissueextract. By whole-mount immunostaining analysis, signal was detected in the regions of inter-somites, vitelline veins, andbranchial arches at the tailbud stage. Staining of Rdd was remarkably reduced in the embryos injected with vascular endothelialgrowth factor Morpholino. We suggest that Rdd proteins interact with a molecule(s) associated with vascular precursor cells.