We have investigated the expression of J1/tenascin in the sciatic nerve of the adult mouse under normal and regenerating conditions by immunocytological and immunochemical methods. In the normal nerve, J1/tenascin expression was confined to the extracellular matrix at the node of Ranvier and in the perineurium. At 2 days after nerve transection, J1/tenascin was detectable in the fibroblast-containing caps of the distal and proximal nerve stumps, in the distal nerve stump along its entire length and in the distal end of the proximal nerve stump. In the nerve stumps immunoreactivity was predominantly associated with extracellular matrix consisting of collagen fibrils and Schwann cell basal laminae. Approximately 7 days after transection, the caps of the nerve stumps had usually grown together forming a bridge. This bridge consisted of a J1/tenascin-negative perineurium-like structure and an inner part of predominantly fibroblasts, endothelial cells and macrophages. All cell types in this inner part were embedded in a J1/tenascin-positive matrix of collagen fibrils indicating the prospective direction of growth of neural elements. A few days later, J1/tenascin in the bridge was confined to the extracellular matrix around small Schwann cell-containing nerve fascicles. In nerves chronically denervated for 19 days, J1/tenascin was poorly detectable in the cap of the distal stump, although Schwann cells had infiltrated this cap. Approximately 19 days after the lesion, J1/tenascin expression returned to control levels in the proximal nerve stump. In the distal nerve stump, J1/tenascin immunoreactivity reached a peak at approximately 14 days after nerve transection and vanished only at approximately 35 days, thus correlating with the time of active regrowth of axons into the distal nerve stump. This reduction was prevented by chronic denervation, suggesting that reinnervation of target structures may be related to the down-regulation of J1/tenascin. These combined observations suggest that J1/tenascin is differentially regulated in the individual parts of the regenerating nerve, possibly triggered by different cellular and molecular signals.