The loss of duodenal folds visible endoscopically has recently been reported as being a marker for celiac disease. We have investigated the sensitivity and specificity of this finding with a prospective study in 75 patients with symptoms or results of investigations compatible with celiac disease. Reported duodenal fold appearance was compared with histological findings, disaccharidase levels, and clinical diagnosis. Fifteen patients were found to have celiac disease and 11 had reduced or absent duodenal folds compared with only 2 of 60 patients who did not have celiac disease (p less than 0.0001). This finding has a sensitivity of 73%, specificity of 97%, and positive predictive value of 85%. Duodenal folds were not reported as being abnormal in seven patients with hypolactasia or two with giardiasis and did not appear to be influenced by age. A reduction in the number or height of duodenal folds as seen endoscopically in the second part of the duodenum is a specific and sensitive sign of celiac disease. Endoscopists should biopsy the duodenum for celiac disease whenever the duodenal folds appear to be reduced or absent.