Left forelimbs of postmetamorphic Xenopus laevis froglets were repeatedly denervated prior to and following amputation. Amputations were performed 14, 21, 28, or 42 days after the original denervation. A tissue-regenerative response resulting in the formation of a spike-shaped, heteromorphic outgrowth was found in the sham-denervated and control animals, but dedifferentiation of the stump tissues was not apparent. Tissue-regenerative outgrowths were not observed in the denervated cases; instead, dermal wound healing and stump and scar formation occurred. In both control and experimental cases, however, a periosteal proliferative response to amputation injury led to the development of a greatly thickened periosteum the length of the amputated radius-ulna as well as a cap of cartilage at the distal end of these bones. We conclude from these results that forelimbs of postmetamorphic froglets are incapable of adjusting to a prolonged nerveless state sufficient to allow the normal tissue-regenerative response of spike outgrowth formation.