Soluble CD44 is present in the serum of normal individuals (2.7 +/- 1.1 nM). The concentration of soluble CD44 in the serum is elevated in patients with advanced gastric (24.2 +/- 9.8 nM) or colon cancer (30.8 +/- 11 nM). Serum CD44 concentration correlated with tumor metastasis and tumor burden. Surgical resection of tumors resulted in decreases in serum CD44 levels. By Western blot analysis, monoclonal anti-CD44 antibody reacted with a major protein with molecular weight between 130,000 and 190,000. In addition, two proteins with molecular weights of 72,000 and 80,000 can also be identified. Therefore, different CD44 isoforms may be present in the serum of cancer patients. Serum CD44 concentrations may be an indicator of tumor burden and metastasis in patients with malignant diseases.