Serum glycyl-l-prolyl 4-methyl-coumaryl-7-amide (gly-pro-MCA) hydrolase (DPP IV) and L-lysyl-L-alanyl beta-naphthylamide (lys-ala-beta NA) hydrolase (assumed to be DPP II) activities were measured in patients with oral squamous cell carcinoma and healthy subjects. The mean serum DPP IV activity of all cancer patients was significantly (P less than 0.001) decreased, compared with that of healthy subjects. Although there was no significant difference between the stages by International Union Against Cancer (UICC) classification (1978), DPP IV levels tended to change dynamically, reflecting the clinical status during therapies. The serum DPP IV activity of patients with a fair prognosis was significantly elevated toward the normal range, whereas the activity of patients with a poor prognosis was significantly decreased (P less than 0.05). In contrast, the mean serum lys-ala-beta NA hydrolytic activity of cancer patients was significantly (P less than 0.001) increased, compared with that of healthy subjects, and was changed reciprocally to DPP IV activity. The correlation of these two serum enzyme activities with tumor weights also was observed in animal models using nude mice transplanted with human KB carcinoma cells and hamsters transplanted with BHK21 cells. These results indicate that these serum enzyme levels may become an aid for the diagnosis of malignant tumors and for estimating the prognosis of the patients.