In this study, the kidney analog of the erythrocyte anion exchanger, band 3, served as the first example of an anion translocating membrane protein in a nucleated cell type to be localized at the ultrastructural level. Kidney band 3 was found to be confined to the basolateral membrane of the intercalated cells in the human collecting duct. The immunogold label displayed a striking non-uniform distribution along the basolateral plasma membrane with a preferential concentration at pleated areas of the membrane surface. The pleated portions are suggested to represent specialized subdomains to which the band 3 analog might be restricted by linkage via ankyrin to the spectrin-based membrane cytoskeleton. The immunolabel did not extend apically to the level of the zonula adherens and zonula occludens indicating that tight junctions might not be important for maintaining the polarized distribution of this integral membrane protein. Association of antibody label with the rough endoplasmic reticulum and other types of cytoplasmic membranes indicate pathways in the biosynthesis and degradation of this anion exchanger.