To arrive at a basic understanding of the pathogenesis of reflux esophagitis, we developed an acute experimental model in the rabbit for studying the early lesion. Acid was perfused in vivo into the lower esophagus while potential difference was monitored intermittently. At varying degrees of potential difference decline, indicating epithelial injury, the esophageal stratified squamous epithelial tissue was removed for morphologic studies and in vitro electrophysiologic and transport studies. At 50 per cent reduction in potential difference, there was dilation of intercellular spaces, which when correlated with physiologic results of increased permeability indicates increased intercellular water. At 100 per cent reduction in potential difference, cells in the midepithelium were observed to be swollen and ruptured, forming vesicular spaces, midepithelial cleavages, and later early ulceration. Results of functional studies at this stage showed inhibition of sodium transport. The midepithelial site of disruption corresponds to the site of active sodium pumping out of cells in other stratified squamous epithelia. Since sodium is transported by esophageal epithelium and this function was inhibited by acid, we propose that this early morphologic lesion may be the result of damage to the sodium-transporting mechanisms of the epithelium.