The transformation of a normal cell through dysplasia to the malignant state usually is associated with changes at the molecular level within the nucleus, cytoplasm and cell surface. These changes can be monitored by the loss of normal cell surface antigens, such as the blood group antigen ABO(H) and major histocompatibility complex antigens, which in the human correlate with the histocompatibility locus antigens. A group of patients with bladder biopsy and diagnosis ranging from normal through severe dysplasia to papillary transitional cell carcinoma, invasive transitional cell carcinoma and carcinoma in situ were evaluated for the presence or absence of beta-2-microglobulin. This 11,000 molecular weight protein was used as an indirect marker for the major histocompatibility complex antigens on the cell surface. With immunoperoxidase as a marker, the presence of beta-2-microglobulin was seen in all patients with normal epithelium as well as benign disease. However, with progression through dysplasia to carcinoma there was progressive deletion of the beta-2-microglobulin. Carcinoma in situ exhibited minimal expression of the beta-2-microglobulin. The use of beta-2-microglobulin as a marker for major histocompatibility complex antigens on the cell surface may prove to be useful for monitoring transitional cell carcinoma.