Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into "foreign" denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory.(ABSTRACT TRUNCATED AT 400 WORDS)