The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective response measure, patients receiving preoperative radiotherapy followed by cystectomy were studied. Pretreatment tumour samples and clinical data from 108 consecutive patients were collected. End points were complete response (CR) to radiotherapy, relapse-free survival time and overall survival time. Expression of pRB was assessed by immunohistochemical staining as present or absent. Complete response to radiotherapy was obtained in 42 of 106 evaluable patients (40%). Predictive for CR to radiotherapy, in univariate analysis, was transurethral resection (as opposed to biopsy), B-haemoglobin, no upper urinary retention, and loss of pRB staining. Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor. Loss of pRB was the only parameter showing statistically significant, independent association with relapse-free survival, whereas B-haemoglobin was also independently associated with overall survival. Loss of pRB expression seems to indicate a phenotype displaying enhanced radiosensivity and may be of benefit by denoting patients who would selectively benefit from a treatment schedule containing radiotherapy.