The neurotransmitter histamine (HA) is involved in central regulation of secretion of prolactin (PRL) and the proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), β-endorphin (β-END) and α-melanocyte-stimulating hormone (α-MSH). The effect of HA on POMC-derived peptides and PRL release is, at least in part, indirect and may involve activation of catecholaminergic systems. Therefore, we investigated the effect of β-adrenergic receptor blockade on HA or HA agonist-induced release of ACTH, β-END, α-MSH and PRL. Central administration of HA, the H₁-receptor agonist 2-thiazolylethyramine (2-TEA) or the H₂-receptor agonist 4-methylhistamine (4-MeHA) stimulated the secretion of ACTH, β-END, α-MSH and PRL. Pretreatment with the P-adrenergic antagonist propranolol inhibited secretion of the POMC peptides in response to HA, 2-TEA or 4-MeHA. Propranonol only inhibited the PRL response to HA or 2-TEA, but had no effect on the PRL response to 4-MeHA. Administration of the β-receptor agonist isoproterenol stimulated ACTH, β-END, α-MSH and PRL two to five-fold. This effect was totally blocked by pretreatment with propranolol. We conclude that HA-induced secretion of POMC-derived peptides from the anterior and intermediate lobe of the pituitary gland and of PRL from the anterior lobe is, at least in part, mediated via catecholamines. β-Adrenergic receptors are involved in the mediation of the POMC response to H₁- as well as H₂-receptor activation, whereas β-receptors are involved only in the mediation of the PRL response to H₁-receptor activation.