Although gastro-esophageal reflux (GER) is one of the major causes of chronic persistent cough (CPC) in the USA and in Europe, it is a rare cause of CPC in Japan. We report a rare case of CPC caused by GER, in which treatment with an H2-blocker or with a proton pump inhibitor was successful. A 65-year-old woman had complained of coughing for over 25 years. Her coughing was not alleviated by treatment with a bronchodilator (beta 2-adrenoceptor agonist), an anti-allergic agent, a corticosteroid, or a sedative. GER was considered as a possible cause of her coughing because exacerbation of the coughing was associated with the development of gastrointestinal symptoms (heartburn). Fiberoptic esophagoscopy showed esophagitis and esophageal herniation of the sliding type. Twenty four-hour monitoring of distal esophageal pH showed that the coughing occurred when the pH dropped below 4, and that the pH was less than 4 for about 7% of the whole monitoring time. An H2-blocker or a proton pump inhibitor completely eliminated the symptoms. Therefore, CPC caused by GER was diagnosed. We found that coughing could be induced by instillation of 0.1 N hydrochloric acid at the distal esophagus, and that the coughing was partially inhibited by inhalation of an anti-muscarinic agent (ipratropium bromide) and by esophageal instillation of 4% xylocaine. These data support the "reflex theory". Although CPC caused by GER is rare in Japan, we should remember that GER can be a cause of CPC even in Japanese patients.