Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.