We investigated the immunohistochemical localization of inositol 1,4,5-trisphosphate receptor (IP(3)R) Types 1, 2, and 3 in rat airway epithelium using the monoclonal antibodies KM1112, KM1083, and KM1082 specific for each type of IP(3)R, The epithelium from trachea to distal intrapulmonary airways (bronchioles) showed positive immunoreactivity for all types of IP(3)R, However, cell type as well as subcellular site immunoreactivity for each type of IP(3)R varied, IP(3)R Type 1 was found only in the apical thin cytoplasmic area of ciliated cells throughout all airway levels. IP(3)R Type 2 was exclusively localized to the entire cytoplasm of ciliated cells from the trachea to bronchioles, IP(3)R Type 3 was expressed mainly in the supranuclear cytoplasm not only of ciliated cells at all airway levels but also in Clara cells of the bronchiolar epithelium. Double fluorescent staining using combinations of KM1083 and Wisteria floribunda lectin or anti-rat 10-KD Clara cell-specific protein antibody confirmed that the IP(3)R Type 2-positive cells were neither seromucous cells nor Clara cells, These results indicate that the expression of three types of IP(3)Rs in different cell types and subcellular sites may reflect diverse physiological functions of IP(3)Rs within airway epithelial cells, The double staining studies suggested that the anti-IP(3)R Type 2 monoclonal antibody KM1083 would be a specific cell marker for ciliated cells of the airway epithelium.