The Los Angeles classification of reflux oesophagitis includes sharply demarcated areas of erythema without any associated slough within the definition of reflux-induced mucosal breaks, though there is uncertainty as to whether these "red streaks" actually represent such a mucosal lesion. This study evaluates the histopathology of these red streaks. Forty patients with one or more red streaks on the tops of the mucosal folds in the distal oesophagus were included in a multinational, multicentre prospective study. All patients were referred for upper gastrointestinal endoscopy to investigate chronic heartburn and acid regurgitation. Biopsies were taken from the red streaks and from control biopsies from more normal appearing mucosa 1 cm lateral to the red streaks. A two-sided probability test using normal approximation assessed differences in the histological findings at the two biopsy locations. Compared to control biopsies, biopsies of red streaks had a significantly thicker basal cell layer (mean +/- s 41% +/- 32% versus 18% +/- 23% of mucosal thickness, P=0.001) and longer papillae (mean +/- s 71% +/- 19% versus 49% +/- 24% of mucosal thickness, P= 0.001). Of the red streak biopsies, 25% had either newly re-epithelized lesions or granulation tissue beneath squamous epithelium. Only 10% of the control biopsies had moderate or more marked regenerative changes (based on elongation of papillae and basal cell hyperplasia), compared to 65.1% of red streak biopsies. Of the biopsies from the red streak itself, 7% showed no abnormality and 27.9% only slight changes. In comparison, 25% of the biopsies from control biopsies showed no regenerative changes and 62.5% only slight change due to gastro-oesophageal reflux disease. The histomorphological counterpart to the endoscopically visible red streaks of the distal oesophagus is marked regenerative changes of the squamous epithelium and/or capillary rich granulation tissue beneath the squamous epithelium. Red streaks are validated as being indicative of acid/peptic mucosal injury, but they do not satisfy a strict definition of a mucosal break.