The studies reported here addressed the effects of chronic administration of thyroxine (2 mg/liter for 60 days) on catalepsy and the functional activity and expression of the 5-HT1A and 5-HT2A receptor genes in the brains of adult male mice of the cataleptic ASC strain and the catalepsy-resistant AKR strain. Thyroxine induced cataleptics in AKR mice but had anticataleptic activity in ASC animals. Chronic thyroxine administration increased the functional activity and expression of 5-HT2A receptors in the frontal cortex in AKR mice but not in ASC mice. In ASC mice, the hormone significantly weakened the hypothermic effect of the 5-HT1A receptor agonist 8-OH-DPAT, though it did not alter the expression of these receptors. These results suggest that 5-HT2A receptors are involved in the cataleptogenic while 5-HT1A receptors are involved in the anticataleptic effects of the hormone in mice.