AIMS: To investigate the immunohistochemical expression of p53 and bcl-2 proteins in squamous cell carcinoma (SCC) of the oesophagus and to assess whether expression of these oncoproteins can be used to stratify patients into groups with a favourable or unfavourable response to preoperative chemo/radiotherapy. METHODS: The initial diagnostic biopsy and the corresponding resected samples were obtained from 22 consecutive patients with SCC. All patients underwent preoperative chemo/radiotherapy. Tumour sections were incubated with a monoclonal antibody directed against p53 (DO-7). Twenty four non-neoplastic oesophageal biopsy specimens immunostained for p53 served as controls. Twelve randomly chosen sections from the 22 SCC samples were immunostained to test for bcl-2 protein expression. RESULTS: After chemo/radiotherapy, 12 (55%) of the 22 patients had no evidence of tumour in the resected oesophagus. Before chemoradiotherapy, however, 17 (77%) patients were p53 positive. After treatment, residual carcinoma was detected in seven (41%) of the 17 p53 positive patients. All non-responsive cases had the same p53 immunopattern as before treatment. Bcl-2 immunoexpression was detected in six (50%) of 12 patients. Residual tumour was detected in the residual oesophagus in two (33%) of the six bcl-2 positive patients. After treatment, bcl-2 expression was no longer detected in the residual neoplastic cells of a previously bcl-2 positive tumour. Using Fisher's exact test no significant association was found between oncoprotein expression and response to preoperative treatment. CONCLUSION: This study confirms the observation that p53 protein is frequently expressed in SCCs of the oesophagus, probably as a result of a mutation of the TP53 gene. However, no significant association was found between oncoprotein expression and response to chemo/radiotherapy. Anticancer agents do not seem to modify the expression of p53 and bcl-2 proteins.