Abstract Heartburn is the most typical gastro-oesophageal reflux disease (GERD) symptom. The transient receptor potential vanilloid receptor-1 (TRPV1) is a candidate mediator of heartburn. Exposure of TRPV1 to capsaicin is characterized by activation, followed by desensitization. Our aim was to investigate the effect of intra-oesophageal capsaicin instillation on oesophageal symptom perception (activation) and on sensitivity to oesophageal acid perfusion and oesophageal balloon distention (desensitization). In a first protocol (n = 10), saline or capsaicin solution were instilled in the mid-oesophagus and symptoms were rated at 5-min intervals for 60 min. In a second study (n = 10), oesophageal 0.1 N hydrochloric acid perfusion was performed 60 min after pretreatment with saline, low or high dose capsaicin. In a third study (n = 10), sensitivity to oesophageal balloon distention was determined before and at 30-min intervals up to 90 min after pretreatment with saline, low or high dose capsaicin. Areas under the curve (AUC) for symptom intensities under different conditions were calculated and compared with Kruskal–Wallis test. Oesophageal capsaicin instillation induced transient symptoms of retrosternal and epigastric burning in a dose-dependent fashion. After oesophageal capsaicin or saline instillation, there was no difference in symptom pattern and intensities induced by oesophageal acid perfusion. After oesophageal capsaicin or saline instillation, sensitivity to oesophageal balloon distention and oesophageal compliance were not significantly altered. Oesophageal instillation of the TRPV1 receptor agonist capsaicin induces symptoms of retrosternal and epigastric burning in a dose-dependent fashion. Pretreatment with capsaicin does not desensitize the oesophagus to acid perfusion or to balloon distention.