We examined the matrix metalloproteinase (MMP) activity and tumor necrosis factor (TNF)-alpha in luminal fluid of 18 extravasation mucoceles and in saliva from Wharton's duct of five patients by means of gelatin zymography and enzyme immunoassay, respectively. The luminal fluid showed a high level of MMP activity compared with the saliva. Quantitative determination by enzyme immunoassay revealed that the luminal fluid contained higher levels of TNF-alpha than the saliva. In addition, the amount of TNF-alpha in luminal fluid exhibited a direct correlation with MMP activity estimated by densitometric analysis of gelatin zymograms. Since TNF-alpha stimulates the production of MMPs from cells such as fibroblasts, these results suggest that TNF-alpha is one of the causal molecules that enhance the accumulation of proteolytic enzymes in luminal fluid of mucoceles.