Recent studies have shown the accumulation of high levels of p53 protein to be associated with malignant disease, within a range of tissues. This paper assesses p53 expression in oral mucosal disease. Biopsies were obtained from a range of oral disorders which included normal, benign, premalignant, and malignant oral tissue. In addition, oral smears were obtained from a limited number of patients with biopsy-proven oral cancer. Expression of the p53 protein was assessed using the polyclonal antibody CM1, together with a standard immunoperoxidase technique. A total of 37 oral cancers were assessed, of which 20 were found to express the p53 protein (54 per cent of cases). The p53 protein was not identified in normal, benign, or premalignant oral mucosa (54 cases). The identification of p53 within biopsies of oral mucosal lesions would appear to correlate with oral malignancy.