Distal regeneration in Ciona intestinalis involves the proliferation of adult stem cells residing in vasculature of the branchial sac and the migration of progenitor cells to the site of injury and regeneration. However, after the Ciona body is bisected, regeneration occurs in the proximal but not in the distal body fragments, even if the latter include a part of the branchial sac with stem cells. A transcriptome was sequenced and assembled from the isolated branchial sacs of regenerating animals, and the information was used to provide insights into the absence of regeneration in distal body fragments. We identified 1,149 differentially expressed genes. The hsp70, dnaJb4, and bag3 genes were among the highest upregulated genes, defining a stress response that is essential for regeneration. This study demonstrates the importance of a stress response for stem cell activation and the promotion of regeneration in Ciona, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates.