<p>Ptychodera flava is a hemichordate whose anterior structures regenerate reproducibly from posterior trunk pieces when amputated. We characterized the cellular processes of anterior regeneration with respect to programmed cell death and cell proliferation, after wound healing. We found scattered proliferating cells at day 2 of regeneration using a proliferating cell nuclear antigen antibody. On day 4, most proliferating cells were associated with the nerve tract under the epidermis, and on day 6, a small proboscis derived from proliferated cells was regenerated, and a mouth had broken though the epidermis. TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) detected elevated levels of apoptosis in the endoderm that began furthest away from the region of wound healing, then moved anteriorly over 8 days. Posterior to anterior apoptosis is likely to remove digestive endoderm for later differentiation of pharyngeal endoderm. We hypothesize that P. flava regeneration is nerve dependent and that remodeling in the gut endoderm plays an important role in regeneration.</p>