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Objective: Crocin and safranal, as the major constituents of saffron, have many biological activities. This study investigated the effects of crocin and safranal on yawning response induced by intracerebroventricular (i.c.v.) injection of histamine in rats. Materials and Methods: In ketamine/xylazine-anesthetized rats, a guide cannula was implanted in the right ventricle of the brain and yawning induced by i.c.v. injection of histamine. Crocin and safranal were intraperitoneally (i.p.) injected alone and before i.c.v. injection of histamine. Results: Histamine at the doses of 10 and 20 µg/rat produced yawning. Mepyramine (a histamine H1 receptor antagonist) 40 µg/rat significantly (p