In the Barrett's oesophagus (BE) progression from metaplasia, via dysplasia, into invasive cancer, an aberrant cell proliferation governed by genetic change plays a central role. Alterations of the p53 tumour-suppressor gene appear especially critical and, like the proliferation marker Ki67, can be detected by immunohistochemistry. The purpose of this study therefore was to investigate the clinical value of p53 and Ki67 as markers for tumour progression in BE, and at the same time test the validity of the concept of a metaplasia-dysplasia-carcinoma sequence in BE by correlating the expression of these markers with various grades of dysplasia. Thirty-two lesions (seven negative for dysplasia, five indefinite for dysplasia, 11 low-grade dysplasia and nine high-grade dysplasia) from 25 archival resection specimens were selected for study. Increasing grades of dysplasia showed increasingly p53 accumulation; p53 accumulation was never observed in mucosa without dysplasia. The increasing p53 expression was accompanied by an increased Ki67-labelling index and an upward shift of the proliferative compartment. The results lend support to the multistep progression model of a metaplasia-dysplasia-carcinoma sequence in BE. Expression of p53 and Ki67, markers which can be easily applied on archival material, can be valuable adjuncts for the histopathological diagnosis of dysplasia and may have predictive value for cancer risk.