An abnormal thyroid status induces morphological and neurochemical modifications in the adult brain. In this study we have analyzed the expression of enkephalin (ENK) and dynorphin (DYN) precursor mRNAs by means of in situ hybridization in the brain of hypothyroid and hyperthyroid rats. The influence of thyroid hormones on kainic acid (KA)-induced expression of ENK and DYN mRNAs in the granule cells of the dentate gyrus was also studied. Our results can be summarized as follows: (1) hypothyroidism induces an up-regulation of ENK mRNA in the granule cells of the dentate gyrus and layers V/VI of the cingulate cortex and of DYN mRNA in the granule cells of the dentate gyrus; (2) the up-regulation of ENK mRNA expression in the granule cells induced by KA is not modified by altered thyroid status; (3) in contrast, the KA injection fails to up-regulate DYN precursor mRNA expression in the granule cells of the rostral dentate gyrus of the hypothyroid rats; (4) injection of KA in hyperthyroid rats increases the expression of DYN mRNA in the granule dentate gyrus more than in euthyroid rats. The present results suggest that thyroid hormones exert an inhibitory control of expression of ENK and DYN mRNAs in selected brain areas. This effect could be directly mediated though the thyroid hormone nuclear receptor or could be secondary to changes in glutamatergic transmission in the dentate gyrus, as suggested by the profound alteration of the KA-induced expression of DYN mRNA in the dentate gyrus of hypo-and hyperthyroid rats.