As bacillus Calmette-Guérin (BCG) immunotherapy is highly effective for most but not all superficial bladder tumors, there is a need to define predictors of response to this mode of treatment. We have investigated a panel of markers defined by monoclonal antibodies, directed against tumor-associated transitional cell carcinoma antigen (G4 and E7), epidermal growth factor receptor, cytokeratin (CK) 18 and blood group antigens A, B and H, using an indirect immunoperoxidase staining on paraffin sections. Twenty superficial bladder tumors (T1) treated with intravesical BCG therapy (10 responders and 10 nonresponders) were tested with this panel. Among the responders, expression of CK18 antigen was positive in 7 and negative in 3, whereas in the nonresponder group it was positive in 2 and negative in 8. The difference was statistically significant (p less than 0.05). Loss of expression of CK18 antigenicity was associated with recurrence or progression of superficial bladder tumors following BCG therapy, indicating that changes in CK patterns should be investigated as potential predictive markers for response to BCG.