The natural history of duodenal lesions was studied in 20 patients with familial adenomatosis coli/Gardner's syndrome. These patients were followed for an average of 7.1 yr (range 1 yr, 7 mo to 12 yr, 2 mo) and repeatedly examined by hypotonic duodenography, duodenofiberscopy, and biopsy. Tubular adenomas of the duodenum (less than 8 mm in diameter) were present in 18 (90%). During the follow-up period, there was a slight increase or decrease in the number of duodenal adenomas in 4 patients but no distinct change in 13. In the remaining patient (aged 49 yr), a polypoid lesion (17 mm in diameter) of the duodenal bulb, which had been overlooked at the initial examination, became an advanced cancer (50 x 30 mm in size) during 22 mo. Tubular adenomatous tissue of the duodenal papilla was detected in 11 patients (55%). Follow-up study of the lesions revealed no change in endoscopic and histologic findings in all but 1 patient, in whom there was a slight enlargement of the duodenal papilla, as seen at endoscopy. These findings suggest to us that in patients with this disease, duodenal adenomas do not require prophylactic surgery. However, careful repeated follow-up examinations with endoscopic biopsy should be performed, with endoscopic removal of larger polyps when possible.