Interleukin-8 (IL-8) production by the gastric mucosa is increased in Helicobacter pylori infection. Previous studies indicated that H. pylori induces IL-8 synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production is supposed to be associated with cagA and other cag pathogenicity island genes, including picB gene. In the present study, we investigated the induction of IL-8 in primary cultures of normal human gastric epithelial cells to elucidate the IL-8 induction by wild type strains and by the picB knockout strain. Human gastric epithelial cells were obtained from surgically resected specimens from four patients. Three H. pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1; isogenic picB mutant of TN2F4, Tx30a; type 2 strain) were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels in culture medium were determined by enzyme immunoassay. Human gastric epithelial cells produced IL-8 at a 10-50 times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 at significantly lower levels than the parent strain. Cells from four patients behaved similarly on IL-8 production. The results of the present study demonstrated the induction of IL-8 in normal gastric epithelial cells, suggesting that picB gene product may play an essential role in vivo.