The IS substance (molecular weight: 52,000, pI: 2.7-3.3) levels in the serum was examined in patients with various diseases. The IS substance levels in patients with gastric, colorectal, biliary-pancreas and esophageal cancer were significantly higher than those in healthy volunteers. The level of IS substance increased in accordance with advance of cancer, showing the highest level in advanced and recurrent cancer patients. In benign disease patients, high levels of IS substance were also observed in the serum of infectious diseases and chronic renal failure. In contrast, patients with liver cirrhosis had a definite low level of IS substance. When the IS substance level was compared with other parameters in cancer patients, a definite correlation was found with immunosuppressive acidic protein and alpha 2 globulin. However, there was no correlation with skin reaction, lymphocyte number, T-cell number, or PHA induced lymphocyte blastgenesis. It is suggested that the IS substance level is a useful indicator to judge the extent of disease before operation and to estimate the clinical course after operation.