It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)