Twenty-nine patients (20 men, nine women; mean age, 65.9 years; range, 49-77 years) with intraductal papillary mucinous neoplasms associated with so-called "mucinous ductal ectasia" of the pancreas were studied both histochemically and immunohistochemically. These cases included six cases of hyperplasia, 13 adenomas, and 10 adenocarcinomas. The mean sizes of the hyperplasia, adenomas, and adenocarcinomas were 2.0 cm, 3.0 cm, and 4.8 cm in diameter, respectively. Tumor size correlated with the degree of cellular atypia. The proliferative rates were significantly higher in the carcinomatous epithelium with those in the hyperplastic and adenomatous epithelia. The polarity of distribution of carcinoembryonic antigen and carbohydrate antigen 19-9 were better preserved in the hyperplastic epithelia than in the carcinomatous epithelia. On the other hand, the papillary and nonpapillary hyperplastic epithelium contained mainly a neutral periodate-reactive glycoprotein with only trace amounts of sialomucins and sulphomucins. In addition, the adenomatous epithelium contained mostly sialomucins with a small amount of sulphomucins. The carcinomatous epithelium contained predominantly sulphomucin. The results of both the histological and immunohistochemical studies suggested the possibility of a sequential change from nonpapillary and papillary hyperplasia, via adenoma, to carcinoma in intraductal papillary-mucinous neoplasms associated with mucinous ductal ectasia. Moreover, these results, in combination with the histochemical findings, are considered helpful in making an appropriate preoperative diagnosis with endoscopic pancreatic ductal biopsy specimens, thus enabling the surgeon to select the most appropriate surgical procedure.