Most previous studies of Barrett's metaplasia have used biopsy material to document cell, gland, and architectural types, leading to inaccurate or incomplete conclusions. The present study presents data from eight esophagogastrectomy specimens of Barrett's metaplasia with associated neoplasia, which were evaluated topologically by use of dissecting microscopy, specimen radiography, scanning electron microscopy, and routine histologic examination. Barrett's metaplasia was found to be mosaic of cell, gland, and architectural types, showing variable degrees of atrophy and maturation toward intestinal and gastric epithelium. Zonation was not found. Surface mucous, goblet, absorptive, mucous neck, mucous gland, and neuroendocrine cells were found in all cases; Paneth, chief, and parietal cells were found in approximately half. The presence of villar architecture with lining goblet and absorptive cells is unique and can be used to make a biopsy diagnosis. In one case, only a minute residual focus of Barrett's metaplasia was found, suggesting that the pathogenesis of some cases of adenocarcinoma of the lower esophagus and gastric cardia unassociated with Barrett's metaplasia may be the same. Nine cases of adenocarcinoma of the gastroesophageal junction unassociated with Barrett's metaplasia, studied during the same time period, had similar epidemiologic characteristics including mean age, age range, and sex distribution. Multifocal dysplasia and carcinoma in situ were found in all but one case. In two of eight cases adenomatous change was present; one of these resembled a villous adenoma of the colon with malignant degeneration. Barrett's metaplasia thus appears to be important as a precursor of adenocarcinoma in the region of the lower esophagus and gastroesophageal junction. The significance of these findings in relation to previous reports is discussed.