While the activation of the proto-oncogenes has been implicated in the development and progression of cancer of many tissues, the role of oncogenes in the development of oesophageal adenocarcinoma has not been defined. Fifteen patients who had undergone resection for oesophageal adenocarcinoma and 15 who had undergone oesophagectomy or biopsy for Barrett's oesophagus were studied. The latter patients also had adjacent normal gastric mucosa biopsied for comparison with the metaplastic oesophageal mucosa. The mucosal samples were snap frozen and subsequently stained with monoclonal antibodies to the following oncogene associated proteins; c-erbB2 (neu and CE-1) (external domain), c-erbB2 (NCL-CB11) (internal domain), c-src, c-ras, c-myc, c-fos, c-jun, and the onco-suppressor gene--p53. All tumours were well or moderately differentiated adenocarcinomas arising from the lower third of the oesophagus. Eleven specimens showed strong membraneous staining with both c-erbB2 (neu) and c-erbB2 (CBL-CB11). Seven specimens showed strong nuclear staining with p53 onco-suppressor gene. Three specimens were positive for c-ras and c-src, and two were positive for c-jun. In Barrett's epithelium, nine specimens were positive for c-erbB2 (neu and CB11), three were positive for c-src, two were positive for c-ras and c-jun, and one was positive for c-fos. Two of the gastric mucosal biopsy specimens expressed c-erbB2 weakly but no other oncogenes were found. The frequency of positive staining for c-erbB2 is very high, compared with the expression of these genes in other tumours. It is also concluded that errors in the onco-suppressor gene p53, and especially in the external and internal domains of c-erbB2, which is also often expressed in Barrett's mucosa, may be implicated in the development of adenocarcinoma of the oesophagus.