Background Previous studies have demonstrated that a single 30-minute distal esophageal infusion of concentrated (0.15M, pH 0.8) hydrochloric acid (HCl) induces hyperalgesia to an electrical stimulus in a human model. The aim of this study was to refine this model using physiological acid concentrations (pH: 1.8-4) in repeated short exposures. Methods Two different cohorts of 10 volunteers underwent 2 studies. Study 1: randomization to 4 x 5-minute distal esophageal infusions of acid (0.15M) or saline, 1-hour apart. Double-blind measurements of baseline and post-exposure proximal esophageal and chest wall pain thresholds (PTs) were performed to electrical stimulation at 30-minute intervals throughout the study. Study 2: randomisation to 4 x 15-minute infusions of 0.15M, 0.075M, 0.01M HCl and saline. Results Study 1: With multiple acid infusions, a significant progressive drop in PTs was observed in both areas tested (P<0.0001). Study 2: Increasing acid concentrations had a significant effect over multiple time points P < 0.0001. Similar initial reductions in PTs were observed for all acid concentrations compared to saline, however hypersensitivity was shorter lasting with 0.01M acid. Conclusions In healthy subjects, esophageal hypersensitivity can be induced and maintained up to 4 hours by repeated short-duration acid infusion and at physiological pH levels. This has implications for future model design and pathophysiological understanding of acid-related esophageal hypersensitivity.