Interleukin-18 (IL-18), a cytokine that promotes Th1 responses, is processed to the active mature protein by caspase-1. The effects of Helicobacter pylori infection on gastric IL-18 and caspase-1 were examined. In antral mucosa, IL-18 mRNA expression was greater (P<.01) in H. pylori-positive (n=40) than in H. pylori-negative patients (n=29) with normal mucosa. Inactive precursor (24 kDa) and mature (18 kDa) IL-18 were present in antral biopsy specimens from uninfected and infected subjects. In corpus mucosa, mature IL-18 and a 16-kDa protein, corresponding to inactive IL-18, were present. Active caspase-1 p20 subunit was detected in antral and corpus mucosa of infected and uninfected subjects. These data show that, although H. pylori infection is associated with increased antral IL-18 mRNA expression, mature IL-18 protein and active caspase-1 p20 are present in mucosa of both H. pylori-infected and -uninfected subjects. IL-18 may have an important role in promoting gastric Th1 responses in H. pylori infection.