Thyroid hormones have profound effects on mood and behaviour, but the molecular basis of thyroid hormone action in the adult brain is relatively unknown. In particular, few thyroid hormone dependent genes have been identified in the adult brain despite extensive work carried out on the developing brain. In this work we have performed global analysis of gene expression in the adult rat striatum in search for genomic changes taking place after administration of triiodothyronine (T3) to hypothyroid rats. The hormone was administered in two different schedules: i) a single, large dose of 25 ug/100 g body weight (SD), or ii) 1.5 ug/100 g body weight once daily for 5 days (RD). Twenty four hours after the single or the last of multiple doses, gene expression in the striatum was analyzed using Codelink microarrays. SD caused up-regulation of 149 genes and down-regulation of 88 genes. RD caused up-regulation of 18 genes and down-regulation of 1 gene. The results were confirmed by hybridization to Affymetrix^TM microarrays and by TaqMan PCR. Among the genes identified are genes involved in circadian regulation and in the regulation of signalling pathways in the striatum. These results suggest that thyroid hormone is involved in regulation of striatal physiology at multiple control points. In addition, they may explain the beneficial effects of large doses of thyroid hormone in bipolar disorders.