Helicobacter pylori (Hp) is highly associated with duodenal (DU) and gastric ulcer (GU). However, the exact pathophysiological mechanisms are not yet clear. Distribution of Hp in stomach and duodenum may differ for DU and GU. To study the presence and density of Hp in untreated patients with DU (n = 49; mean age 54.4 yr, 33M) or GU (n = 47; mean age 63.4 yr,22M ), two biopsy specimens of normal-looking duodenum, antrum and corpus, and of the ulcer were obtained for histology. Serial sections were stained by modified Giemsa (MG) and immunohistochemistry (IMM) (DAKO B471) against Hp and graded semi-quantitatively as 0, 1, 2 or 3. Hp was found in 40 (81.6%) of DU and in 39 (80.9%) of GU patients using IMM. In DU patients, 39 (79.6%), 38 (77.6%), 8 (16.7%) and 4 (40.0%) of corpus, antral, duodenal and ulcer biopsies were Hp-positive by IMM. Median gradation per positive biopsy was 1, 2, 2, and 1, respectively. In GU patients, 35 (79.5%),34 (72.3%), 10 (22.2%) and 27 (65.9%) were Hp-positive by IMM with median gradations of 2, 2, 1, and 2, respectively. Mean pH of gastric juice was 2.0 (n = 41) for DU and 2.9 (n = 39) for GU. Comparing MG with IMM, concordance concerning Hp was found in 98.0% of DU and 87.2% of GU. In only 6 DU and 8 GU patients were non-Hp bacteria assumed by joint evaluation of MG and IMM.Conclusion: Comparably high prevalences of Hp were found in antrum and corpus for both DU and GU, but a low prevalence was found in the duodenum. In DU the density of Hp was higher in the duodenum, but in GU the density was higher in the corpus. These differences may contribute to different pathophysiological mechanisms.