The locus of the inhibitory action of histamine on cold-stimulated TSH secretion was studied in male rats. Various histaminergic drugs were given either into the median eminence (ME), the third ventricle, the rostral and caudal part of anterior hypothalamus (rAH and cAH) or the posterior hypothalamus (PH) of conscious rats. When infused into ME, histamine (5 and 10 micrograms/rat) decreased and mepyramine (2.5 micrograms) increased the cold-stimulated TSH secretion while a larger dose of mepyramine (10 micrograms/rat), impromidine (0.05 and 0.1 microgram/rat), 2-pyridylethylamine (2-PEA; 5 and 10 micrograms/rat) and cimetidine (2.5 and 7.5 micrograms/rat) had no effect. The inhibitory action of histamine (5 micrograms/rat) was most marked 30 min after the infusion into ME and it remained significant for at least 50 min. Neither cimetidine (50 and 100 mg/kg i.p.) nor mepyramine (10 and 20 mg/kg i.p.) antagonized the inhibitory action of histamine (5 micrograms/rat) in ME. Histamine (10 micrograms/side) inhibited the cold-stimulated TSH secretion likewise when infused bilaterally either into rAH, cAH or PH. TSH secretion induced by exogenous TRH (100 ng i.p.) was also inhibited by histamine (1 microgram/rat) given into the third ventricle. In conclusion, histamine seems to have an inhibitory action on the cold-stimulated TSH secretion. This action is apparently mediated through areas close to the third ventricle. The mechanism of this action seems to be fairly non-specific, i.e. it is mediated through neither H1- nor H2-receptors.