The possible involvement of histamine (HA) in the stress-induced increase in plasma renin activity (PRA) was investigated in male rats. Intracerebroventricular (ICV) infusion of histamine (HA; 3.8–60 µg) increased PRA dose-dependently, and the K<sub>d</sub> (dissociation konstant) of HA was estimated to approximately 30 µg. ICV infusion of HA (30 µg) as well as 5 min of restraint stress increased plasma renin activity (PRA) 2- and 3-fold, respectively (p < 0.01). These effects were abolished by prior ICV infusion of the H<sub>2</sub>-receptor antagonists cimetidine (100 µg) and ranitidine (125 µg) (p < 0.01), which reduced the PRA to subbasal levels (p < 0.05). When administered alone the H<sub>2</sub>-receptor antagonists had no effect on PRA. In contrast, the H<sub>1</sub>-receptor antagonist mepyramine (100 µg) increased the basal PRA level (p < 0.01) and slightly augmented the HA- and stress-induced increase in PRA (p < 0.05). HA as well as restraint stress increased the plasma levels of dopamine, norepinephrine and epinephrine almost 2-fold (p < 0.01). The effect of the two stimuli was prevented by prior ICV infusion of mepyramine or cimetidine (p < 0.01). Pretreatment with the β-adrenergic receptor blocker propranolol (7 mg/kg i.p.) abolished the HA-induced and inhibited by 70% the stress-induced PRA increase. The results indicate that histaminergic neurons participate in the cerebral regulation of renin secretion. The H<sub>2</sub>-receptor-mediated PRA-increasing effect of HA involves activation of sympathetic nerves. In addition, HA seems to exert a minor inhibiting effect on PRA via H<sub>1</sub>-receptors.