TAG-1 is a member of the immunoglobulin superfamily of cell adhesion molecules thought to play important roles in neuronal differentiation and the establishment of connectivity during brain development. Because these are processes also affected by hypothyroidism, we studied the effects of thyroid hormone deprivation and administration on TAG-1 expression in the developing rat brain. By in situ hybridization, immunohistochemistry and Western blotting we found that TAG-1 RNA and protein levels are upregulated in the hypothyroid brain. From embryonic day 20 to postnatal day (P) 15, elevated TAG-1 RNA was found in several areas including the cerebral cortex, hippocampus and olfactory bulb. In agreement with this, TAG-1 protein was overexpressed in the major fibre tracts arising from these structures, including the corpus callosum, anterior and hippocampal commissures and lateral olfactory tract. A similar overexpression of TAG-1 by hypothyroidism was detected in the cerebellum, but starting only at P15. In all cases, elevation of TAG-1 RNA and protein expression could be reversed by thyroid hormone treatment. These results show that the deregulation of TAG-1 might contribute to the alterations caused by the lack of thyroid hormone during brain development.