Aim/Background Lye (NaOH) ingestion in humans often results in alkaline damage to the esophagus, but knowledge about this process is limited. Here, we explore the effects of lye on esophageal epithelial structure and function using rabbit esophageal epithelium as a model of lye ingestion. Methods Rabbit esophageal epithelium was mounted in Ussing chambers so that the electrical potential difference (PD), short-circuit current (I (sc)), and transepithelial resistance (R (T)) could be monitored before, during, and after mucosal exposure to lye (NaOH) at pHs ranging from 7.4 to 12.1. Histopathology and dextran fluxes were also performed and correlated with the electrical data. Results Mucosal exposure to lye at pHs < 11.5 had no damaging effects on the esophagus. However, at pHs a parts per thousand yen11.5, damage was both time- and pH-dependent, as noted by increases in PD and I (sc), and declines in R (T). Further, the electrical changes were paralleled morphologically by epithelial liquefaction necrosis and increases in dextran flux. Also, by pretreating tissues with ouabain, the early lye-induced rise in PD and I (sc) was shown to result from a combination of increased active (sodium) transport and passive (sodium) diffusion which indicates that, even early on, the damaging effects of lye include changes in both apical cell membranes and tight junctions of this epithelium. Conclusion Lye (NaOH) injury to the esophageal epithelium is both pH- and time-dependent, but requires a minimum pH of 11.5. At pHs a parts per thousand yen11.5, lye produces liquefaction necrosis, an injury that involves both cellular and junctional barriers, and which markedly increases epithelial permeability to ions and uncharged molecules. Based on these results, non-industrial cleaning products in the home are likely to be safer if they have a concentration of lye below pH 11.5.