We investigated the role of adrenergic receptors in histamine (HA)-induced release of corticotropin (ACTH) and prolactin (PRL) in conscious male rats. Specific α- or β-receptor antagonists were administered intracerebroventricularly in doses of 1 mmol at time -20 min, and HA (270 nmol), the H₁ receptor agonist 2-thiazolylethylamine (2-TEA; 2180 nmol) or the H₂ receptor agonist 4-methylHA (4-MeHA; 790 nmol) were administered intracerebroventricularly at -15 min. The animals were decapitated at 0 min, and plasma was analyzed for ACTH and PRL. Administration of HA and the histaminergic agonists stimulated ACTH secretion equally, while only HA and the H₂ receptor agonist stimulated PRL secretion. Pretreatment with the adrenergic receptor antagonists had no effect on the ACTH response to the histaminergic compounds. In contrast, the PRL response to HA or 4-MeHA was inhibited or prevented by the α-receptor antagonists phenoxybenzamine and phentolamine, the α₁-receptor antagonist prazocin, the β-receptor antagonist propranolol and the β₁-receptor antagonist atenolol, whereas the α₂-receptor antagonist yohimbine or the β₂-receptor antagonist ICI-118-551 had no effect. The study indicates that histaminergic neurons interact with the catecholaminergic neuronal system in regulation of PRL secretion, and that this interaction is dependent upon activation of α₁- and β₁-receptors. In contrast, histaminergic neurons stimulate ACTH secretion independently of adrenergic receptor activation.