The soluble fragment of E-cadherin protein (S-ECD) is reported to be increased in the peripheral blood of cancer patients. In this study, we investigated the clinical significance of serum S-ECD in 81 patients with gastric cancer. The amount of serum S-ECD was significantly higher in the gastric cancer patients (4735 +/- 2310 ng ml(-1)) than in healthy volunteers (2515 +/- 744 ng ml(-1)). With the normal range cut-off at average +2 s.d., 67% patients showed abnormally high serum S-ECD levels. This frequency was significantly higher than that of other tumour markers, such as CEA (4.4%) or CA19-9 (13.3%). However, there was no significant correlation between the amount of S-ECD and clinicopathological factors. Serum S-ECD might be derived from cancer tissue, as removal of cancers by surgical treatment results in quick decline of the serum S-ECD and S-ECD can be detected by immunoblot in cancer tissues but not in normal epithelium. The serum S-ECD amount was compared with the E-cadherin expression in cancer tissues, which were classified into those showing preserved (+), partially reduced (+/-) or lost (-) expression. Interestingly, E-cadherin (+/-) tumours showed higher serum S-ECD levels than the other types, and a higher amount of S-ECD in the immunoblot analysis. Thus, the serum level of S-ECD may serve as an excellent tumour marker with high sensitivity. Furthermore, analysis of S-ECD in serum and cancer tissue can offer clues for elucidating the mechanism of reduction of E-cadherin expression in cancer cells.