A,B blood group antigens in tissues of AB heterozygotes. Emphasis on normal and neoplastic urothelium. The tissue distribution of the A and B blood group antigens was studied in 41 individuals with the heterozygous AB red blood cell (RBC) phenotype. A total of 134 biopsies from a variety of normal tissues (94 from urothelium and 40 from other tissues) were examined. In addition, changes in the expression of these antigens associated with neoplastic transformation were evaluated in 70 biopsies from transitional cell carcinomas of 19 AB heterozygous patients. There was heterogeneity in the distribution of tissue A and B antigens, depending on the cell type, as well as among cells of the same type. Ninety-one percent of AB heterozygotes expressed both A and B antigens in normal epithelial cells, with a mosaic distribution clearly apparent in 50% of these individuals. In 21% of these subjects, the A antigen was undetectable in the vascular endothelial cells in all biopsies from several organs. In most (79%) transitional cell neoplasms, only one of the two antigens was consistently expressed. The results of this study may have implications for the clonal or specific gene deletion theories of neoplasia. They also demonstrate the existence of a subgroup of AB individuals in whom the A antigen is absent specifically from the vascular endothelium. 