Proteinases are known to be involved in carcinogenesis, and various substrates are now available to measure the activity of these enzymes. No suitable serum tumour marker for head and neck squamous cell carcinoma (HNSCC) exists at this moment. Therefore, we compared proteinase-activity in serum of 20 untreated HNSCC patients with that of 20 non-cancer individuals. When N-benzoyl-DL-arginine-beta-naphtylamide (BANA) was used as the substrate, proteinase-activity seemed higher among patients, but this difference disappeared after adjustment for alcohol and tobacco consumption. Applying N-a-benzoyloxycarbonyl-L-arginyl-L-arginine-7-amido-4-methylcou marine (ZAAM) as the substrate no difference was found. Addition of E-64, an inhibitor of cysteine proteinase showed that cathepsin B contributed minimally to the ZAAM-specific activity.