Regeneration of the arm of the star¢sh, Asterias rubens (L.) (Echinodermata: Asteroidea) was examined using two preparations. The ¢rst involved regeneration of the entire arm tip and its associated sensory structures and the second examined regeneration of a small section of radial nerve cord in the mid-arm region. Cell cycle activity was investigated by incorporation of the thymidine analogue, bromodeoxyuridine (BrdU). Details of neuroanatomy were obtained by immunocytochemistry (ICC) using an antiserum to the recently isolated star¢sh neuropeptide, GFNSALMFamide (S1). BrdU labelling indicated that initial events occur by morphallaxis, with cell cycle activity ¢rst apparent after formation of a wound epidermis. As regeneration proceeded, BrdU immunoreactive (IR) nuclei revealed cell cycle activity in cells at the distal ends of the radial nerve cord epidermis, in the coelomic epithelium, the perihaemal and water vascular canal epithelia, and in the forming tube feet of both preparations. By varying the time between BrdU pulses and tissue ¢xation, the possible migration or di¡erentiation of labelled cells was investigated. Neuropeptide ICC indicated the extension of S1-IR nerve ¢bres into the regenerating area, soon after initial wound healing processes were complete. These ¢bres were varicose and disorganized in appearance, when compared to the normal pattern of S1-IR in the radial nerve. S1-IR was also observed in cell bodies, which reappeared in the reforming optic cushion and radial nerve at later stages of regeneration. Double labelling studies with anti-BrdU and anti-S1 showed no co-localization in these cell bodies, in all the stages examined. It appeared that S1-IR cells were not undergoing, and had not recently undergone, cell cycle activity. It cannot be con¢rmed whether S1-IR neurons were derived from proliferating cells of epithelial origin, or from transdi¡erentiation of epithelial cells, although the former mechanism is suggested. Di¡er-entiation of the regenerating structures to replace cells such as S1-containing neurons, is thought to involve cell cycle activity and di¡erentiation of epithelial cells in the epidermal tissue, possibly in association with certain types of coelomocytes which move into the regenerating area.