Stress is an important trigger for IBS-symptoms and preclinical investigations suggest that barrier- and sensitivity changes may relate to stress-induced degranulation of intestinal mucosal mast cells.[2]–[4] A recent clinical trial with the mast cell stabilizer and histamine-1-receptor (H1R) antagonist ketotifen confirmed the possible relevance of this cell type.[5] Ketotifen not only decreased abdominal pain and other IBS symptoms but also improved health related quality of life and increased the threshold of discomfort in hypersensitive patients. The gene discussed is HRH1; the disease is irritable bowel syndrome.