Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.) carcinoma. Moreover, the measurement of TAG-72 may also be clinically useful in discriminating malignant from benign effusions. Serum TAG-72 and CEA levels were evaluated longitudinally in a series of patients following resection of primary G.I. carcinomas. A consistent relationship between efficacy of the surgery and serum TAG-72 clearance was observed, and TAG-72 alone or in combination with CEA accurately predicted recurrence of malignant disease in greater than 90% of the patients. The results indicate that TAG-72 is a new human serum tumor marker which, measured alone or in combination with other well established markers, may improve the diagnosis and/or clinical management of malignant disease.