NGFI-A is an immediate-early response gene induced by signals that initiate growth and differentiation. Its mRNA encodes a sequence-specific transcriptional activator possibly implicated in the control of brain developmental processes. Due to the essential role of thyroid hormone for a correct brain development, we have now investigated the possible regulation by 3,5,3'-triiodo-L-thyronine (T3) of NGFI-A gene expression during maturation of the central nervous system. Our results indicate that expression of mRNA encoding NGFI-A transcription factor is about 8-fold decreased in the brain of neonatal hypothyroid rats. No changes were seen when hypothyroidism was induced in adult life. T3 treatment increased NGFI-A mRNA within 1 h, suggesting that thyroid hormone effect is likely to be a direct one. These data indicate a strong regulation by thyroid hormone of the expression of the growth factor inducible gene NGFI-A during brain development, making this gene a suitable model to study T3 action in the early developing nervous system.