The subcellular distribution of the blood group antigen A in the transitional epithelium of the urinary tract and its neoplastic growths was studied using transmission immuno-electronmicroscopy. Sixty-five tissue specimens from 50 blood group A1 patients were processed according to an immunogold procedure which was optimized for preservation of both antigen and ultrastructure. The reactions were stronger in the glycocalyx of the luminal surfaces and at the interdigitating cytoplasmic processes of the cells. In the intracellular compartment the reactions were associated with tubulovesicular membrane-bound structures and with the Golgi complexes. Secretory products, intra- or extra-cellular, were also positive. The greatest variability was noted in the cell surface reactions, which were positive in 88% of normal but only 41% of neoplastic urothelial specimens. An inverse correlation was found between malignant behaviour and cell surface, but not intracellular, reactions. We conclude that, in transitional cell carcinomas, there is a quantitative defect in the processing of substance A which affects predominantly the cell surface component and may involve either the transport-insertion steps, the plasma membrane-associated glycosyltransferases or internalization of blood group antigen A.