We prospectively evaluated the value of histology in identifying gastroesophageal reflux disease (GERD) in consecutive patients enrolled for upper endoscopy. GERD was defined as heartburn occurring at least weekly. Macroscopic esophagitis was graded and an esophageal biopsy was taken 2 cm above the gastroesophageal junction. Histological esophagitis was identified by: (1) basal cell hyperplasia >15%, (2) increased papillary length >66%, and (3) infiltration by leukocytes/eosinophils. The sensitivity, specificity, and positive and negative predictive value of histological esophagitis in patients with and without typical reflux symptoms, with and without endoscopic changes, or both were evaluated. Of 178 patients, reflux symptoms were present in 59% (N = 105) and esophageal erosions in 19% (N = 34); 75 patients had reflux symptoms but no erosions. While the specificity of histology was adequate (78%), it was insensitive (30%). The positive and negative predictive values were 67% and 44%, respectively. No single individual parameter was better than any other. Thus, histology appears to be of no additional value in identifying GERD.