The effect of prolonged administration of the cytokine interleukin (IL)-1beta on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in Wistar rats. In addition, we examined the effects on the proliferating cell nuclear antigen (PCNA) labeling index and the hepatocyte growth factor (HGF) immunoreactivity of the gastric mucosa. The rats received intraperitoneal injections of 0.1 or 0.3 microg/kg body weight of IL-1beta every other day after oral treatment with MNNG for 25 weeks. Long-term administration of IL-1beta at high dose, but not at low dose, significantly increased the incidence of gastric cancer in week 52. Administration of IL-1beta at high dose also significantly increased the labeling index and the HGF immunoreactivity of the gastric antral mucosa, and induced inflammatory cell infiltration and glandular atrophy of the gastric mucosa. Because IL-1beta production in the gastric mucosa is increased in patients with Helicobacter pylori-associated gastritis and eradiation of the organism significantly decreases the IL-1beta production, these findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be in part mediated through IL-1beta.