Forty patients with choledochal cysts, 17 children and 23 adults, were treated by cyst excision in this institution (1972 to 1982). Histochemical and immunohistochemical studies were performed on tissue from the walls of these 40 cysts. The type and degree of histologic changes observed were found to correlate with patient age at time of cyst excision. Specimens from four patients less than two years of age at time of excision revealed epithelial desquamation, fibrosis, and minimal evidence of inflammation. Among specimens from 13 patients, 4 to 15 years of age, only two had an intact epithelial lining. Marked inflammation and intramural glandular structures were observed. Specimens from 23 patients, more than 15 years of age at the time of cyst excision, showed marked acute or chronic inflammation and destruction of the epithelial lining. In this age group, intramural glandular structures with goblet and argyrophil cells were regularly observed within the cyst walls, and gastrin and somatostatin-like immunoreactivity was detected in cells of these metaplastic glands. In association with these changes, in five of the 23 patients in the oldest age group, adenocarcinomas were observed in the cyst walls. These studies establish the increasing rate of epithelial metaplasia in the walls of choledochal cysts with advancing age, and suggest that these changes are a continuing process with malignancy one of the end results.