Abstract High levels of histamine are found in the hippocampus. The central histamine system is involved in many physiological behavioural processes including anxiety-related behaviours both in animals and humans. In the present study, we investigated the effects of intra-hippocampal CA1 (intra-CA1) microinjection of histaminergic agents on anxiety-related behaviours in rats, using elevated plus-maze test of anxiety. Intra-CA1 administration of histamine (at the dose of 10 μg/rat) increased open arm time (%OAT) and open arm entry (%OAE) but not locomotor activity, thus showing an anxiolytic response. Intra-CA1 microinjection of pyrilamine (H 1 receptor antagonist; at the doses of 10, 20 and 40 μg/rat) in combination with histamine (10 μg/rat) showed a decrease in the %OAT and %OAE. Higher dose of the antagonist (40 μg/rat) by itself increased both %OAT and %OAE, but not locomotor activity, indicating an anxiolytic effect. Intra-CA1 microinjection of ranitidine (H 2 receptor antagonist), at the doses of 10, 20 and 40 μg/rat, also reduced the histamine response. Furthermore, the H 2 receptor antagonist by itself reduced %OAT and %OAE without affecting locomotor activity. The results may indicate an anxiogenic effect for the antagonist. Our results showed that histamine may modulate anxiety via H 1 and H 2 receptors in the CA1 region of hippocampus of the rat.