Previous investigations showed that the morphological basis of the low- threshold rapidly adapting mechanoreceptors in the salamander skin is the neurite-Merkel cell complex located in the epidermis. We have now examined whether sensory nerves are required for the appearance of Merkel cells, and whether these cells act as specific targets for ingrowing sensory axons. Electronmicroscopic examination of denervated skin shows that Merkel cells survive in normal density and appearance in the epidermis for at least six months without nerves. In addition, mechanosensory function of such skin is restored when the skin becomes reinnervated either by collaterally sprouting (intact) nerves or by regenerating ones, and Merkel cells are then found to have nerve terminals associated with them. These experiments suggest that Merkel cells do act as targets for ingrowing nerves in these circumstances. Further experiments were done on skin that had regenerated in the total absence of any innervation to the limb; such new skin contained nerve-free Merkel cells that were normal in appearance, density and location. When nerves were allowed to innervate this new skin the sensory axons grew to the ‘new’ Merkel cells and established typical neurite-Merkel cell complexes, and normal mechanosensory function. Since the new skin had developed without nerves, the sensory axons were not following ‘old’ pathways to the Merkel cells. We conclude that the Merkel cells are the true targets for the mechanosensory axons; these cells attract the sensory axons to them and/or contain specific markers that allow the ingrowing axons to recognize them. Once a Merkel cell becomes innervated it loses this ‘target cell’ quality. In addition, mechanosensory function of the sensory endings appears to occur only when the endings have developed a morphological association with a Merkel cell.