Effects of calcium hopantenate (HOPA) on the hypothalamic pituitary-thyroid axis in rats were studied. Basal plasma thyrotropin (TSH) levels significantly decreased from 277 ± 24 to 167 ± 24 ng/ml (p < 0.01) at 20 min after HOPA administration. In the bicuculline-pretreated rats, the inhibitory effect of HOPA on TSH release was corrected. The plasma immunoreactive thyrotropin-releasing hormone (TRH) and TSH responses to cold were significantly inhibited after HOPA administration. The plasma TSH response to TRH was also significantly inhibited by HOPA. The plasma thyroxine and 3,3’,5-triiodothyronine levels did not change after HOPA administration. Findings suggest that HOPA acts both on the hypothalamus and pituitary gland, inhibiting TRH and TSH release.