Tumor cells and urine-voided cells from patients with invasive bladder carcinoma as well as from healthy patients were examined cytologically, ultrastructurally and immunocytochemically. The ultrastructure of tumor cells showed an abundant, dilated, rough endoplasmic reticulum in the form of membrane-bound vacuoles full of granular to fibrillar material located perinuclearly and/or paranuclearly. Some cells exhibited enlarged modified lysosomes containing sparce flocculent and particulate precipitate. Papanicolaou staining of these cells showed two basophilic cytoplasmic textures, one green glossy-patchy, perinuclearly and/or paranuclearly, well segregated from the other texture of peripheral hematoxylinophilic foamy cytoplasm, comparable to the cytologic features of cell cultures originating in invasive bladder carcinoma. PAS diastase showed double distribution and texture of the perinuclear glycosaminoglycans, a glossy accumulated mass and large granules. Glycosaminoglycan sacs similar to those of cell cultures were also present in tumor-dispersed cells. There was a nonspecific binding of antisera against lysozyme, human chorionic gonadotropin and alpha 1-trypsin in normal and tumor cells. Tumor cells and tissues were positive for alpha 1-chymotrypsin distributed perinuclearly and in large spheres. Normal cells lacked the above characteristics. The results indicate that it is feasible to use the aforementioned characteristics in conjunction with the existing bladder-cytologic criteria for malignancy as markers in urothelial cancer with regard to prognosis of superficial tumors with high malignant potential.