Abstract.The mechanisms of acid damage to oesophageal epithelium are incompletely understood. In particular, it is unclear whether luminal acid enters and damages the oesophageal epithelium by traversing the paracellular and/or transcellular route. The present paper describes studies of the role of serosal bicarbonate ions (HCO3−) in oesophageal protection against acid damage, the results of which have direct implications regarding the route of H+entry. The results indicate that HCO3−protects by buffering H+within the intercellular compartment of the extracellular space, and that this protection can be mimicked almost completely by replacement of serosal HCO3−with HEPES (N‐2‐hydroxyethylpiperazine‐N′‐2‐ethane sulphonic acid), a buffer that cannot permeate cells. These findings support the hypothesis that luminal acid damages oesophageal epithelium primarily by H+diffusion through the par