TNF has diverse biological effects including a role in the immune response and growth regulatory effects.OBJECTIVES: The aim of this study was to determine the nature and location of cells able to synthesise and respond to TNF in oral mucosa in health and disease.MATERIALS AND METHODS: The location of immuno‐reactive TNF and 55‐kDa and 7s‐kDa TNF receptors was demonstrated using immunohistology. We also used RT‐PCR to help determine the sites of synthesis of this cyto‐kine in oral mucosa.RESULTS: Only occasional TNF‐positive cells were detected in normal epidermis and oral mucosa. However, this cytokine was found throughout the epithelia in oral lichen planus, leukoplakia and squamous cell carcinoma (SCC). The possible cellular sources and biological effects of TNF in these disease processes is discussed. The 55‐kDa TNFR was expressed at the cell membrane throughout the epidermis, but confined to the lower cell layers on oral mucosa. Ten of 22 SCC did not express this receptor. A significant correlation was observed between the velocity of tumour growth and absence of TNF receptors.CONCLUSIONS: The growth inhibitory and immuno‐regulatory effects of TNF may be modulated by changes in receptor expression and alterations in synthesis of this cytokine in a subgr