In order to characterize T cell responses in human Helicobacter pylori infection, we have examined proliferative responses and cytokine production by CD4⁺ and CD8⁺ T cells isolated from duodenal ulcer patients and asymptomatic H. pylori carriers, after activation with some H. pylori antigens that may be important in disease development. For control purposes, T cells from uninfected volunteers were also examined. The different H. pylori antigens induced only modest proliferative responses in circulating CD4⁺ and CD8⁺ T cells from both H. pylori-infected and uninfected individuals. However, circulating T cells from H. pylori-infected subjects produced larger amounts of interferon-gamma (IFN-γ) in response to the Helicobacter antigens than did T cells from uninfected volunteers. Furthermore, CD8⁺ T cells produced larger amounts of IFN-γ than did CD4⁺ T cells, on a per cell basis. Most IFN-γ-producing cells from both infected and uninfected volunteers appeared to be naive T cells expressing CD45RA. Increased production of IL-4 and IL-5 was, on the other hand, only seen in a few instances after stimulation of isolated CD4⁺ and CD8⁺ T cells. Stimulation of freshly isolated gastric T cells with the different H. pylori antigens did not result in increased proliferation or cytokine production. In conclusion, our results show that several different purified H. pylori antigens induce production of IFN-γ, preferentially by CD8⁺ cells. Therefore, they suggest that IFN-γ-secreting CD8⁺ cells contribute significantly to the cytokine response induced by H. pylori infection.