In a search for genetic markers of duodenal ulcer, serum pepsinogen I level, ABO blood groups and secretor status were determined in 89 siblings of 34 duodenal ulcer families. Duodenal ulcer patients were likely either to have hyperpepsinogenemia I or to be non-secretors on a familial basis, but not to have an increased frequency of blood group O. The frequency of duodenal ulcer in the siblings was highest in hyperpepsinogenemia I/non-secretor and lowest in normopepsinogenemia I/secretor. Therefore, the influence of two genes, hyperpepsinogenemia I and non-secretor, on the risk of duodenal ulcer is multiplicative. These results provide evidence on the hypothesis of polygenic inheritance of duodenal ulcer.