This study investigated genetic differences between Helicobacter pylori-positive and -negative duodenal ulcer patients. Seventy-two patients with duodenal ulcer (61 H. pylori positive and 11 H. pylori negative) were examined for HLA-DQA1 genotype. The allele frequency of DQA1*0102 was higher in H. pylori-negative than in H. pylori-positive patients. Moreover, the genotypes that possessed the DQA1*0102 allele were significantly more common in H. pylori-negative than in H. pylori-positive patients. In contrast, the allele frequency of DQA1*0301 was lower in H. pylori-negative than H. pylori-positive patients. The genotypes that possessed DQA1*0301 were significantly more common in H. pylori-positive than in H. pylori-negative patients. These results suggest that there are genetic differences between H. pylori-positive and -negative duodenal ulcer patients and that immunogenetic factors for susceptibility or resistance to H. pylori infection exist in the host.