Some reports indicate that morphine can induce anxiolytic effects both in animal and in man. It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine‐induced anxiolysis in rats, using elevated plus‐maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 μg/rat) also increased anxiety‐related behaviours. Intracerebroventricular injection of pyrilamine, a H₁ receptor antagonist (25, 50 and 100 μg/rat), increased anxiety whereas injection of ranitidine, a H₂ receptor antagonist (5, 10 and 20 μg/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H₂ receptors, while the response of H₁ blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 μg/rat), pyrilamine (50 μg/rat) and ranitidine (5 μg/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 μg/rat), pyrilamine (25, 50 and 100 μg/rat) or ranitidine (5, 10 and 20 μg/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety‐related indices in the elevated plus‐maze. This may imply that morphine‐induced anxiolysis probably is independent of the histaminergic system.