The presence of histamine (HA) in the hypothalamus, especially in its median eminence, as well as results of previous studies from this laboratory, suggest a participation of this amine in the regulation of TSH (thyroid stimulating hormone, thyrotropin) secretion. In the present investigation, rats were treated with a single injection of cimetidine (CIM - 100 mg/kg ip), an H2-HA receptor antagonist. In vitro release of TSH in response to hypothalamic extracts from control animals, was approximately 20% smaller when evoked from pituitaries obtained from CIM-treated, rather than control animals. The addition of hypothalamic extracts from CIM-treated rats to incubates of pituitaries from either control or CIM treated rats did not significantly change basal TSH secretion, suggesting that TRH (thyrotropin releasing hormone) content was decreased by the anti-histamine treatment. These results point towards a facilitatory role of HA on TSH secretion both at the hypothalamic level where it may interfere with TRH synthesis, as well as at the pituitary level where it may modify TSH response to TRH.