Objective Infection with Helicobacter pylori is associated with gastric cancer, However, a hereditary risk of gastric cancer has also been reported. Hence, we decided to evaluate H. pylori gastritis in relatives of gastric cancer patients in comparison with matched controls. Design Case-controlled study, Methods A total of 237 patients with merely H. pylori gastritis (i.e. not associated with either peptic ulcer or gastric malignancy), and either first-degree (93.7%) or second-degree (6.3%) relatives with gastric cancer, were age- and sex-matched with 237 patients with H. pylori gastritis unassociated with a family history of gastric cancer. From each patient, antral and corpus biopsy specimens were obtained and investigated for degree (lymphocyte/plasma cell infiltration) and activity (polymorph infiltration) of gastritis (score: 0-4). Intestinal metaplasia was recorded as present or absent. Results The results show that relatives of gastric cancer patients have a significantly greater expression of gastritis due to a higher grade of gastritis in the antrum and corpus (P < 0.0001) and a greater activity of gastritis in the corpus (P < 0.0001), Intestinal metaplasia occurs more often in relatives of gastric cancer patients (antrum: P < 0.0001; corpus: P = 0.0237). Conclusion Since the grade of H. pylori gastritis in relatives of gastric cancer patients is significantly higher than in controls, there appears to be a genetic susceptibility influencing the expression of H. pylori gastritis, Eur J Gastroenterol Hepatol 11:717-720 (C) 1999 Lippincott Williams & Wilkins.