Summary:  Purpose: This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)‐deficient and histamine H1 receptor (H1R)‐deficient mice. Methods: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant‐current stimulator and continued until a generalized convulsion was obtained. Results: The development of amygdaloid kindling in HDC‐deficient and H1R‐deficient mice was significantly accelerated compared with that in their respective wild‐type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC‐deficient and H1R‐deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild‐type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R‐deficient mice at the same dose. Conclusions: These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling.