Helicobacter pylori is ubiquitous in Africa, with acquisition in childhood the rule. Despite the prevalence of a virulent strain (in Soweto, most H. pylori organisms are cagA- and vacAS(1)-positive) H. pylori-associated pathology (duodenal ulcer, gastric ulcer and gastric cancer) has a variable, often low distribution in sub-Saharan Africa that does not parallel H. pylori prevalence in the population, suggesting a different natural history from that seen in developed countries. Progression to atrophic gastritis in Africans does not appear to differ from that reported in other regions, but as yet unidentified factors may play a role in inhibiting progression to gastric cancer. Studies have suggested that the specific IgG subclass response to H. pylori is predominately IgG1 (suggestive of a Th2 response), and the Th2 response may provide a protective effect against development of gastric cancer. Host immune mechanisms may be the key to different responses to H. pylori in the developed and developing worlds.