Immunohistochemical expression of the p53 protein was investigated in carcinoma of the gallbladder (n = 13), common bile duct (n = 7) and ampulla of Vater (n = 9) using the polyclonal, CM1, and monoclonal, DO7, antibodies (Novocastra). This was compared with cases of chronic cholecystitis (n = 11) and preneoplastic lesions of the gallbladder (n = 4) and ampulla (n = 3). Nuclear immunostaining for p53 protein was found only in the poorly differentiated adenocarcinomas of the gallbladder (n = 9) and were associated with a shorter patient survival period (median: 18.6 mths). The moderately differentiated adenocarcinomas (n = 4) did not show p53 immunostaining and were associated with a longer median survival period (26 mths). The gallbladder dysplasias and adenoma also had no p53 protein immunoreactivity. The common bile duct carcinomas did not stain for p53. Focal p53 immunoreactivity was present in only one (11%) of the cases of ampullary carcinoma and in one (9%) of chronic cholecystitis. In summary, increased p53 immunostaining was associated with reduced patient survival and found more frequently in poorly differentiated adenocarcinoma of the gallbladder but not in the better differentiated carcinoma, chronic cholecystitis or preneoplastic lesions of the gallbladder. The differences in p53 immunohistological expression between gallbladder, common bile duct and ampullary carcinomas justify further investigation into the molecular mechanisms responsible for their development.