Thyroid hormones are essential for the development and function of the brain and also for the maturation and repair of the peripheral nervous system. In the brain, most of the 3,5,3'-triiodothyronine is locally produced by 5'-deiodination of thyroxine catalyzed by the type 2 deiodinase. The absence of any information about thyroid hormone metabolism in the peripheral nervous system prompted us to study the expression of type 2 deiodinase (mRNA and activity) in the peripheral nervous system. Expression of type 2 deiodinase mRNA was very low in the sciatic nerve of rats until day 5 after birth, then increased from day 10 to 35-45 and gradually decreased afterwards, down to the low basal levels observed in the adult. A lesion of the sciatic nerve in the adult induced an increase in type 2 deiodinase mRNA and activity. After a cryolesion, the stimulation was observed as early as 4 h and mRNA levels increased until 24-48 h, then gradually declined down to basal levels around 28 days, when regeneration and functional recovery were completed. After a permanent transection, up-regulation of type 2 deiodinase persisted in both proximal and distal segments until the end of the experiment (28 days). Transection and cryolesion were also followed by increased type 2 deiodinase mRNA expression in the ipsilateral L4/L6 dorsal root ganglia within 24 h. Both mRNA and activity were found in the peripheral nerve sheaths but not in the internal compartment of the intact or injured nerve. Cultured fibroblasts from the sciatic nerve expressed type 2 deiodinase 4 h after stimulation by 10 microM forskolin, whereas purified Schwann cells did not. The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process.