Hepatocyte growth factor (HGF) is a stromal cell-derived cytokine that can stimulate invasion and metastasis of carcinoma cells. Recent studies have shown that the serum HGF concentration is elevated in patients with gastric cancer and may be a useful disease marker. However, the origin of the elevated serum HGF remains undetermined. We investigated the site of HGF production by analyzing the relationships between the HGF expression in tumor tissues, the serum HGF concentrations and inflammation in patients with gastric cancer. The serum and tissue HGF concentrations were measured by an enzyme-linked immunosorbent assay. The serum HGF concentration was higher than the normal cut-off level (0.57 ng/ml) in 44% of the patients. Surgical removal of the tumor significantly reduced the serum HGF concentration, suggesting that the tumor tissue was responsible for the increase. Western blotting analysis showed that the HGF protein was expressed in 20 out of 22 tumor tissues. The concentration of HGF in the tumor tissue was significantly higher than that in normal gastric mucosa. Significant correlation was found between tissue HGF concentrations and serum HGF concentrations. No significant correlation was found between the serum HGF concentration and white blood cell count or C-reactive protein concentration, indicating that the increase in serum HGF is not due to inflammation related to the tumor. These results suggest that the elevated serum HGF concentration in patients with gastric cancer is mediated by production from the tumor tissue.