A possible interaction of central histaminergic receptors with adrenergic and cholinergic muscarinic neurons in increasing the pituitary-adrenocortical response under stress, assessed indirectly from the corticosterone concentration in blood serum, was investigated in conscious rats. All the drugs were administered intracerebroventriculary, the antagonists 15 to 30 min prior to the agonists. The histamine-induced increase in serum corticosterone levels of stressed rats was considerably antagonized by prazosin, phenoxybenzamine, phentolamine and yohimbine, alpha 1 and alpha 2-adrenergic antagonists. These antagonists abolished or significantly attenuated the corticosterone response to 2-pyridylethylamine (PEA), an H1-receptor agonist, and to dimaprit and 4-methylhistamine(4-MeHA), H2-receptor agonists. Propranolol, a beta-adrenergic blocker, did not substantially change the corticosterone response induced by histamine or histamine H1- and H2-receptor agonists. Similarly, atropine was ineffective in blocking the increase in serum corticosterone responses induced by either histamine or PEA and dimaprit in stressed rats. These results suggest that both alpha 1- and alpha 2-adrenergic receptors, but not beta-adrenergic and cholinergic muscarinic receptors interact with central H1 and H2 histaminergic stimulation of the increased pituitary-adrenocortical response in stressed rats.