Point mutations in the p53 gene have been detected in a variety of human cancers; the mutations are clustered in four "hot-spots" located in the coding region of exons 5, 7, and 8, which coincide with the four most highly conserved regions of the gene. We report the finding of a heterozygous G----C mutation at codon 280 (exon 8), position 2, of the p53 gene in a nasopharyngeal carcinoma (NPC) cell line, originating from Guangdong, a province in the People's Republic of China that leads the world in NPC incidence. A survey of nasopharyngeal tissues and NPC biopsies revealed that 1 out of 12 NPC samples from Hunan, another province in the People's Republic of China with high NPC incidence, had the same heterozygous mutation at codon 280 of p53, and none of 10 biopsies from Taiwan showed a mutation within exons 5-8 of the p53 gene. No other alteration of gene structure, including gross rearrangement or loss of heterozygosity or abnormality of gene expression was detected in NPC cell lines or NPC biopsies. We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases. This result contrasts with the relatively high frequency of p53 mutations associated with several other human carcinomas and suggests the importance of other genes in NPC genesis.