The role of histamine as a neurotransmitter and neuromedulator in many actions of brain is known, but the function of histamine in learning and memory processes hasn’t been clarified. Therefore in this study, effects of i.c.v. microinjection of histamine, pyrilamine (the H1 Receptor antagonist) and cimetidine (the H2- Receptor antagonist) on consolidation of memory are investigated. For this purpose, a cannula is implanted in right lateral ventricle of adult male rats by stereotaxic apparatus. After training of animal by passive avoidance task, histamine (5,10,20 µg/rat), pyrilamine (10,20,50 µg/rat) and cimetidine (1,10,50 µg/rat) are injected into their lateral ventricle. After a 24 hr. period of time, the level of retention memory was measured. The results showed that histamine attenuated the level of consolidation memory and pyrilamine and cimetidine ameliorated it by dose - dependent manner. The ameliorating and impairing effects of these drugs are derived from interaction between histaminergic system with changes of Ach, noradrenalin and serotonine levels in the brain.