The role of mononuclear phagocytes in orchestrating the host responses to Helicobacter pylori is inadequately understood. Therefore, gene expression for the monocyte/macrophage-derived cytokines interleukin (IL)- 1β, IL-6, and tumor necrosis factor (TNF)-α was determined before and during H. pylori infection of rhesus monkeys by use of a highly sensitive quantitative reverse transcriptase polymerase chain reaction. The numbers of molecules of IL-1β, IL-6, and TNF-α mRNA in gastric tissue during early infection (7 weeks) significantly exceeded the preinfection numbers (P < .03). Moreover, the numbers of IL-1β, IL-6, and TNFα mRNA molecules in persistently infected animals (6 years) also were elevated compared with preinfection numbers (P < .02, P = .03, P = .16, respectively). Cytokine gene expression coincided with progressive H. pylori gastritis, confirmed by increased gastritis scores over preinfection scores (P < .005). These findings provide quantitative evidence that H. pylori induces local gene expression of monocyte/macrophage-derived inflammatory cytokines and evokes an innate response in gastric tissue of nonhuman primates.