Monoclonal antibodies were raised against human placental soluble E-cadherins and used in an immunoenzymometric assay to detect soluble E-cadherins in biological fluids. The E-cadherin assay was accurate enough to quantitate the concentration of soluble E-cadherin in the cell culture supernatants. Immunoreactive E-cadherins, identified as existing in the soluble form in normal serum, were shown to have apparent lower molecular mass (approximately 80 kDa) than intact molecules of E-cadherin. We found that the immunoreactive E-cadherin levels in the serum of the studied cancer patients were significantly elevated (mean +/- s.d. 3.80 +/- 2.36 micrograms ml-1, P < 0.0001) when compared with the normal levels (1.99 +/- 0.50 micrograms ml-1). We also found that serum E-cadherin levels in the 22 patients with gastric cancer (3.51 +/- 1.78 micrograms ml-1, P < 0.02) or the 11 patients with hepatocellular cancer (5.55 +/- 3.11 micrograms ml-1, P < 0.001) were significantly higher than those in the 26 diabetic patients (2.33 +/- 1.58 micrograms ml-1). Of the 54 cancer patients, 53.7% exhibited an elevated amount of soluble E-cadherin in serum. Thus, it is evident that soluble E-cadherin in circulation can be used as a prospective tumour marker that accurately reflects the progressive regeneration of E-cadherin at tumour sites, potentially induced by tumour-associated proteolytic degradation.