Esophageal, fundal, antral, and duodenal mucosal biopsies from 10 patients with heartburn were compared with biopsies from 18 patients with dyspepsia but without heartburn or radiographic or endoscopic evidence of peptic ulcer disease, gastric retention, or esophageal stricture. There was a highly significnt correlation between heartburn and antral gastritis and duodentitis (P less than 0.01). It is suggested that histologic reflux changes are determined by the severity of reflux and reparative potential of the esophageal mucosa. Heartburn, on the other hand, is more related to the nature of the refluxed fluid. The fluid most likely to induce heartburn is one containing duodenal fluid, which is also believed to be an important cause of antral gastritis.