Many cancer patients have elevated serum protein and sialic acid (N-acetyl neuraminic acid, NANA) levels. Serial determinations were performed, using serum treated with perchloric acid from 34 patients with widespread metastatic disease. Six of six patients who underwent debulking surgery had a drop in their serum NANA value to normal levels following a transient rise in the immediate postoperative period. Twenty-eight patients received chemotherapy and had serial NANA determinations over periods ranging from 4 to 12 months. Eleven of 28 patients demonstrated tumor regression or stable disease. Ten of the 11 in this group had a drop in their serum NANA level. The remaining 17 patients showed tumor progression, and serum NANA rose in 11 of 12 patients with widespread progression of metastatic disease. This elevation preceded clinical relapse in 8 of the 11 patients. Elevation did not occur in four of five patients with a local site relapse of disease (two chest wall, one lung mass, one brain metastases). Serial serum glycoprotein titers deserve further consideration as a monitor of response to chemotherapy of metastatic disease.