53 expression was assessed in 93 head and neck squamous cell carcinoma patients using CM-1, DO-7, and DO-1 antibodies. Sixty eight percent was found to have positive nuclear staining. The frequency of p53 mutations were investigated in 13 patients using single-stranded conformational polymorphism (SSCP) analysis of DNA fragments that had been amplified by the polymerase chain reaction (PCR). P53 gene mutations were analyzed by SSCP in exons 4 to 7 of 13 patients, and nine were found to have mutations in exon 4; two of these patients also had a mutation in exon 5. In the group of 93 patients, p53 overexpression was found to correlate with the patients' history of heavy smoking (p < 0.01). We also analyzed the drinking and smoking history of 71 of these patients by logistic regression analysis and found that heavy smoking correlates with p53 overexpression (p < 0.05), but heavy drinking was not found to be significant. However when both smoking and drinking histories were assessed together, a correlation was found (p < 0.05). Future work may indicate that specific p53 mutations are associated with patients who have a history of heavy drinking and smoking.