The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning.