Blood group isoantigens can be demonstrated immune-histologically on normal urothelium of the urinary bladder by means of the specific red cell adherence test. In preneoplastic and reactive changes of the urothelium and in dysplasia and carcinoma in situ, there is a loss of these antigens. Ultrastructural investigations of carcinoma in situ demonstrate a loss of normal membrane structures such as tight junctions, desmosomes, and glycocalyx. Of 18 patients with carcinoma in situ of the urinary bladder, 12 achieved tumor remission after topical chemotherapy with doxorubicin hydrochloride. A recurrence of blood group isoantigens was demonstrated in patients who achieved tumor remission. The antigenicity reappears before complete normalization of the urothelium. Ultrastructural investigations demonstrated normalization of cellular membrane structures in the respective biopsies. According to these findings and the current literature, the mechanisms of action of doxorubicin hydrochloride in carcinoma in situ may be due to retardation of cell cycle, cell loss by desquamation, cell death, and decrease of growth fraction.