Tissue sampling is essential for detecting intestinal metaplasia in the distal esophagus (Barrett's esophagus), because symptoms and endoscopy are not reliable in making this diagnosis. The utility of cytology in this process is unknown. All adult patients having elective upper gastrointestinal endoscopy over a 6-month period were invited to participate in a prospective study whose aim was to determine the prevalence of intestinal metaplasia in the distal esophagus in an adult population with diverse upper gastrointestinal symptoms. Clinical data and endoscopic findings were recorded. Brush cytology and biopsy specimens were obtained from both sides of the apparent squamocolumnar junction. The cytology specimens were processed routinely, stained with the Papanicolaou technique, and reviewed blinded to the clinical information and the histological findings in the corresponding biopsy specimens. One hundred fifty-five patients (81 women, 74 men; 137 whites, 11 blacks, 7 others; mean age, 52 years) were included. Glandular epithelium/cells were present on both histology and cytology in 147 specimens. Thirty-two patients (22%) showed intestinal metaplasia on histology. Of the cytology specimens from these 32 patients, 6 contained definite goblet cells (19%), 7 probable goblet cells, and 19 no goblet cells. Goblet cells and probable goblet cells were observed on cytology in 7 and 11 additional specimens, respectively. One was from a patient known to have intestinal metaplasia in the esophagus. Follow-up endoscopy with biopsy was performed in two of these latter 18 patients and did not show intestinal metaplasia. One case of high-grade dysplasia, two of low-grade dysplasia, and three indefinite for dysplasia were diagnosed on histology. All three cases of dysplasia were also identified on cytology. The three indefinite cases on histology were considered reactive in two and unremarkable in one on cytology. Low-grade dysplasia was diagnosed on cytology alone on two cases. Follow-up endoscopy with biopsy was performed in one patient, and low-grade dysplasia was found. Cytology using the Papanicolaou stain is not as sensitive and specific as histology for detecting intestinal metaplasia in the distal esophagus. However, it may be at least as useful as tissue sampling in detecting dysplasia.