Background-Leptin is an important regulator of food intake and energy expenditure. Initially it was thought to be expressed exclusively in and secreted by adipocytes. Recently, leptin expression was also noted in other tissues, including rat gastric mucosa. Information on leptin and leptin receptor expression in the human stomach is lacking. Aim-To investigate expression of leptin and its corresponding receptors in human gastric epithelial cells. Methods-Fundic and antral gastric mucosal biopsies, primary cultures of human gastric epithelial cells, and the human gastric cancer cell line AGS were screened for expression of leptin and diVerent leptin receptor isoform mRNA by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed for localisation of leptin and leptin receptor proteins in gastric mucosa. Results-mRNA of leptin and its four receptor isoforms (huOB-R, long receptor isoform; huB219.1-3, short receptor isoforms) was detected in gastric mucosal biopsies, cultured human gastric epithelial cells, and gastric cancer cells. Immunohistochemistry demonstrated that chief as well as parietal cells were reactive to leptin and leptin receptors. Conclusions-Leptin and leptin receptors are expressed in human gastric mucosa. These findings suggest a paracrine and/or autocrine eVect of leptin on gastric epithelial cell function. (Gut 2000;47:481-486)