The expression of epidermal growth factor receptor (EGFR), c-erbB-2, and c-erbB-3 was examined immunohistochemically in 57 cases of periampullary carcinoma. The percentage of Ki-67-positive cells was also examined in the same tissue, to determine the relationship between the expression of the members of the type I growth factor receptor family and cell proliferation. In carcinoma of the head of pancreas, the percentage of cases with overexpression of c-erbB-3 was significantly higher than with overexpression of c-erbB-2 and EGFR. In contrast, in lower bile duct carcinoma and carcinoma of the ampulla of Vater, the percentages of cases with overexpression of c-erbB-2 was greater than with overexpression of other growth factor receptors. A higher percentage of cases with overexpression of c-erbB-3 in pancreatic head carcinoma and overexpression of c-erbB-2 in carcinoma of the ampulla of Vater was found in Ki-67 antigen-positive cases. Moreover, the overexpression of c-erb-3 in pancreatic head carcinoma, c-erb-2 in ampulla of Vater carcinoma, and Ki-67 in both carcinomas was found to be associated with poor patient outcome. These results demonstrate that different members of the type I growth factor receptor family are overexpressed in different carcinomas of the periampullary region.