A DNA-binding protein with a molecular weight of 64,000 (64-DP) has been found in elevated concentrations in the serum of patients with malignant diseases, and a quantitative assay system (column-SDS disc electrophoresis method) for it has been developed. The average serum 64-DP level in 49 normal controls was 48 +/- 26 microgram/ml, whereas in 96 patients with untreated malignant disease it was 167 +/- 67 microgram/ml. Sera from patients with non-neoplastic diseases showed normal or only slightly elevated 64-DP concentrations. No organ or tissue specificity seems to be required for malignant growths to result in elevated serum 64-DP concentration. Of particular interest was the finding that all 11 patients with early gastric carcinoma and two patients with early esophageal carcinoma, all having histologically proven pT1 lesions, showed elevated levels of serum 64-DP. Following successful surgical resection and/or chemotherapy, 64-DP tends to fall toward the normal value. Although confirmation must await the results of larger clinical trials, our preliminary results strongly suggest that 64-DP evaluated by the column-SDS disc electrophoresis method may prove to be a useful tumor marker in patients with a wide variety of malignancies.