We have previously reported that short-term LiCl-treatment affects the kinetic characteristics of thyroid hormone binding in adult rat brain (Bolaris, S., Margarity, M., Valcana, T., 1995. Effects of LiCl on triiodothyronine (T3) binding to nuclei from rat cerebral hemispheres. Biol. Psychiatry 37, 106-111); however, the mechanism underlying the above effects of LiCl administration is yet to be determined. In this study, the effects of lithium within one day after its administration (5 mmol/kg BW) on the relative expression of thyroid hormone receptor isoforms and on the cytoplasmic and synaptosomal thyroid hormone availability in adult rat cerebral hemispheres were examined. Although short-term LiCl-treatment did not affect the levels of triiodothyronine either in the synaptosomal or in the cytoplasmic fraction 24 h after LiCl administration, the cytoplasmic availability of thyroxin was lower. In addition, 24 h after the administration of lithium the mRNA levels of the TRalpha1 isoform (T3 binding) increased while the relative expression of the TRalpha2 variant (non-T3 binding) was decreased. Notably, the decrease of the TRalpha2 mRNA levels was also observed 4h after LiCl administration. The expression levels of the TRbeta1 isoform were unaffected in any interval examined. The present study suggests that short-term lithium treatment regulates the relative expression of TRs in an isoform-specific manner and affects the cytoplasmic availability of thyroxin in adult rat brain.