Objective: The endolymphatic sac (ES) is part of the membranous labyrinth of the inner ear. Its central role in immunologic activity within the inner ear has been confirmed by numerous studies. The aim of this study was to investigate the expression of histamine receptors (H1, H2, H3) in the rabbit ES. Methods: A total of 10 healthy male New Zealand white rabbits weighing 2 to 3 kg were used in the experiments. For immunohistochemical studies, immunostaining was performed according to the avidin-biotin-peroxidase complex technique. Results: Serial sections of the ES of rabbits revealed the presence of H1, H2, and H3 receptor immunoreactivity. Immunoreactive cells for all H1, H2, and H3 were found in the epithelial and subepithelial layers of the duct and the proximal ES. In conclusion, this study showed the immunohistochemical localization of H1, H2, and H3 receptors in the ES of rabbits. These receptors may be important in the homeostasis of the inner ear. In addition, they may be target receptors in the medical treatment of inner ear disorders such as endolymphatic hydrops. © 2008.