53 and bcl-2 are involved in the control of cell cycling and apoptosis. Environmental factors such as smoking and radiation can disturb p53 function and predispose a cell to malignant transformation. To investigate the role of p53 mutations, as well as p53 and bcl-2 protein expression in squamous cell carcinoma of the tongue, 39 samples were analysed. Since neck metastasis is the most important prognostic factor of this disease, samples from patients both with and without nodal disease were selected to find out whether there was any difference between the groups. Non-radioactive single-stranded conformation polymorphism (SSCP) was used to screen p53 mutations; an altered SSCP pattern indicating p53 mutation was found in 21 samples (54%). A significant correlation between tumour size, histological differentiation and p53 mutations was found (P < 0.01). Immunocytochemically, nuclear expression of p53 was moderate or strong in 18 (46%) samples. No correlation between altered p53 SSCP pattern and p53 immunoreactivity was seen. bcl-2 expression was cytoplasmic; moderate or strong staining was detected in only six of the carcinoma samples (15.5%). Interestingly, there was a significant correlation between smoking and bcl-2 expression (P < 0.01): all six samples with moderate or strong staining were taken from heavy smokers. Furthermore, all those patients died within 32 months.