It is well known that denervated adults newt limbs do not regenerate. Not understood is why denervated newt limb stumps fail to initiate regeneration upon reinnervation. In an effort to define the regeneration limiting factors, we examined the histology of long-term denervated newt limb stumps and tested the effects of various kinds of reinjury. In 5-week denervated limb stumps there were present dedifferentiated cells, differentiated cartilage, and densely packed layered cells. The epidermis covering the limb tip resembled skin epidermis rather than wound epidermis. The kinds of reinjury that were successful in restoring the regeneration capabilities to 5-week denervated limb stumps included; reamputation (100%), a single razor incision (60%), and removal of the healed tissues from the distal limb tip (70%). The results of the study emphasize the importance of both injury and wound epidermis in initiating regeneration.