A simple procedure is described for the detection of sialic acid in serum. After a direct addition of Ehrlich reagent to serum and an incubation at 56 degrees C for eight hours, the resulting mixture is diluted with saline. After centrifugation, the color in the supernatant is determined at 525 nm in a spectrophotometer. Serum sialic acid was significantly greater in cancer patients than in normals. Cancer patients with metastases had significantly greater sialic acid than cancer patients without metastases. In two cancer patients, sialic acid levels returned to normal after surgery. The diagnostic usefulness of 95.6% was similar to that reported with lipid-soluble sialic acid and seemed to be superior to CEA and other tumor antigens associated with a limited spectrum of tumors. However, patients with inflammatory diseases such as arthritis, Crohn's disease and psoriasis also showed elevated sialic acid levels. Ultrafiltration showed that almost all of the sialic acid was retained on an Amicon filter, which suggests that sialic acid was bound to a macromolecule. A quality control serum run 25 times had a coefficient of variation (CV) of 8.4% and the same serum ran on 42 days had a CV of 11.6%.