Carpal tunnel syndrome represents the most frequent chronic compressive neuropathy in man and hence may be investigated as a spontaneous model of peripheral nerve damage and repair. In the present report the fate of nerve fibers in the digital skin after long-lasting median nerve compression has been investigated immunohistochemically in comparison to normal digital skin, with special consideration to sensory endings and encapsulated receptors. The presence has been documented of the neurospecific marker PGP 9.5, the glia-associated protein S-100, and the neuropeptides CGRP and CPON which are mainly associated with the sensory and sympathetic nerve fibers respectively. The morphology and distribution of nerve fibers and corpuscles appeared comparable to that of normal digital skin; a reduction in the density of sensory receptors has, however, been observed, although not to the degree that was expected to explain the clinical deficits. It has been also demonstrated that at least part of the CGRP-containing sensory and CPON-containing sympathetic axons may survive unaltered even in patients with a long clinical history of profound sensorial impairment. An apparent discrepancy between the maintenance of nerve fibers and the sensory disturbances and the frequent observation of prompt postoperative recovery even after years of compression results from this investigation. The correlation of immunohistochemical observations and functional scores may not be considered conclusive. It must, however, be discussed if the sensorial impairment in this syndrome might have, at least in some cases, not only an anatomical but also an electrophysiological basis.