The possible involvement of the serotoninergic system in histamine-induced PRL secretion was studied in urethane anesthetized male rats. Intracerebroventricular infusion of histamine (30 µg) stimulated PRL secretion 10-fold. This effect was mimicked by the H2-receptor agonist dimaprit (300 µg), while the H1-receptor agonist 2-thiazolylethylamine (140 µg) had no effect. Pretreatment with the serotonin receptor blockers methysergide (2.5 mg/kg i.p.) or ketanserin (2.5 or 10.0 mg/kg i.p.) reduced the PRL peak response to histamine 75, 54, or 58%, respectively. During serotonin receptor blockade, dimaprit had a stimulatory effect similar to that of histamine, while 2-thiazolylethylamine had no effect. Intra-arterial infusion of histamine (420 µg) stimulated PRL secretion 6-fold. This effect was mimicked by the H1-receptor agonist 2-thiazolylethylamine (1,900 µg), while the H2-receptor agonist dimaprit (3,000 µg) had no effect. Pretreatment with methysergide (2.5 mg/kg i.p.) or ketanserin (2.5 or 10.0 mg/kg i.p.) reduced the peak response to histamine 54, 54, or 51%, respectively. The effect of histamine was mimicked by 2-thiazolylethylamine, while dimaprit slightly inhibited the PRL secretion. The antiserotoninergic activity of methysergide and ketanserin was demonstrated by their ability to prevent the PRL-releasing effect to serotonin. The effects of methysergide and ketanserin were not due to dopamine-like activity, since none of the drugs affected basal PRL secretion and since the dopamine receptor antagonist pimozide did not prevent the inhibitory effect of methysergide on the histamine-induced PRL release. The findings indicate that histamine-stimulated PRL secretion is mediated in part by serotoninergic ne