Hypothyroidism may cause peripheral nerve damage, even if the pathophysiology of these changes is still unclear. It has been suggested by some that an increased vascular permeability is involved in hypothyroidism, while others have suggested a "compressive" mechanism caused by mucinous material deposited in the endoneurium. We have studied histologically the endoneurium and evaluated endoneural-vessel permeability in sciatic nerve by means of the leakage of horseradish peroxidase (HRP) in pharmacologically-induced hypothyroidism in rats. We did not find any substantial differences between the hypothyroid group of animals and the controls with respect to endoneural-vessel permeability. In particular, no macromolecular deposits were present in the extracellular space of the endoneurium in either the treated or the control rats. We therefore believe that a "vascular" hypothesis is unlikely for nerve involvement during hypothyroidism, nor was the "compressive" hypothesis supported by our histological findings.