In this study, two different methods were used to investigate the prevalence of columnar-lined (Barrett's) esophagus. First, a population-based study of clinically diagnosed cases was performed in Olmsted County, Minnesota. Twenty-five residents of this county, who had undergone endoscopy and biopsy between 1969 and 1986, were diagnosed as having Barrett's esophagus. On January 1, 1987, 17 of these patients were still living in the county, representing an age- and sex-adjusted prevalence rate of 22.6 cases per 100,000 population (95% confidence interval, 11.7-33.6 cases). A prospective search of Mayo Clinic autopsy material for Barrett's esophagus was conducted using the same diagnostic criteria as in the clinical study. Over an 18-month period ending in September 1987, 7 cases of Barrett's esophagus were found in 733 unselected autopsies. In 5 of the 7 cases, Barrett's esophagus was first detected at the time of autopsy. Using the age- and sex-specific prevalence from the clinically diagnosed study, researchers expected to find 0.19 cases of Barrett's esophagus at the 226 autopsies performed on Olmsted County residents, although 4 were actually observed (P less than 0.001). This approximately 21-fold increase (95% confidence interval, 5-54 cases) corresponds to an autopsy estimated prevalence of 376 cases per 100,000 population (95% confidence interval, 95-967 cases). In conclusion, a majority of cases of Barrett's esophagus, a condition that predisposes to esophageal malignancy, remains unrecognized in the general population.