Helicobacter pylori density was assessed by quantitative culture and histologic examination of gastric biopsy specimens from 29 H. pylori-infected dyspeptic patients. Density was correlated with cagA and vacA genotypes (assessed by polymerase chain reaction and colony hybridization), gastric inflammation and epithelial injury (assessed histologically), and peptic ulceration. Quantitative culture was more reproducible than histology, and antral density was more reproducible than corpus density. Mean antral density of cagA⁺/vaeA s1 strains was 4-fold higher than that of cagA⁻/vaeA s2 strains (1.9 × 10⁶ vs. 4.5 × 10⁵ cfu/g, P = .02). Antral density was associated with mucosal neutrophilic and lymphocytic infiltration (P < .01) and with epithelial injury (P < .05). Mean antral bacterial density was 5-fold higher in duodenal ulcer patients than in others (P = .005). In conclusion, H. pylori density in vivo is easily quantified and is associated with bacterial virulence determinants, gastric inflammation, and duodenal ulceration, suggesting a central role in pathogenesis.