Evaluation of the serum level of immunosuppressive substance in oral cancer patients. The serum level of immunosuppressive substance (IS) was studied in 40 patients with primary oral cancer and in 79 patients without cancer. Its usefulness was evaluated as a parameter for monitoring therapy as well as recurrence of the tumors. Mean values for serum IS in patients with cancer and patients without were 687 +/- 284 micrograms/mL and 464 +/- 153 micrograms/mL, respectively. Normal healthy controls had a mean value of 431 +/- 105 micrograms/mL, with the cutoff value set at 641 micrograms/mL (mean +2 SD). Patients without cancer who had a severe infectious disease showed conspicuously high serum IS levels, and these values were closely correlated with their C-reactive protein values. The positive rate of IS increased in all patients with oral cancer was 58%. The mean level of serum IS in cancer patients was significantly higher than that of the controls (P less than .01), and the level was found to be more elevated as the stage of the disease advanced (stage I to III, 48%; stage IV, 68%). Histologic analysis of the tumor cells in patients with squamous cell carcinoma (SCC) showed that the mean serum IS level of those who had poorly differentiated SCC was much higher (937 +/- 181 micrograms/mL) than that of patients with well-differentiated SCC (616 +/- 159 micrograms/mL). Patients who had recurrent or metastatic cancer, or those who died from the cancer exhibited marked elevation of the serum IS levels, whereas patients who remained free of cancer in the follow-up period showed significantly lower serum IS levels. The rise and fall of the serum IS level was closely correlated with the disease progression and/or remission. These data strongly suggest that serum IS is a useful parameter for monitoring the disease stage as well as the effect of therapy on patients with oral cancer. 