Duodenal polyps and tumours of different histology from patients with familial adenomatous polyposis (FAP) were examined for p53 overexpression to determine the genetic events in duodenal tumorigenesis. Samples from endoscopic biopsy specimens of 152 duodenal adenomatous polyps (taken from 79 patients) and from 13 surgically resected adenomatous polyps or cancers (taken from nine patients) were studied by routine histological examination and immunohistochemistry. p53 was overexpressed in: 0 per cent of normal mucosa samples (none of 29), 25 per cent of tubular adenomas (28 of 111), 72 per cent of tubulovillous and villous adenomas (13 of 18) and 100 per cent of duodenal cancers (seven of seven); and in 28 per cent of mildly dysplastic polyps (32 of 113), 56 per cent of moderately or severely dysplastic polyps (nine of 16) and 100 per cent of cancers (seven of seven). Overexpression of p53 increased with passage down the adenoma-carcinoma pathway and might therefore be a valuable additional marker of risk for duodenal malignancy in patients with FAP.