The incidence of esophageal cancer is extremely high in Linxian County and certain other regions of the People's Republic of China. Epidemiologic and laboratory studies suggest that N-nitroso carcinogens and other environmental factors play a causative role. In the present study, employing over 100 DNA samples obtained from Lin-xian patients who underwent surgery for esophageal cancer, we have found a significant frequency of amplification of either the human epidermal growth factor receptor (HER-I) gene or the c-myc oncogene. These changes were found not only in tumor specimens, but also in adjacent non-tumor (grossly normal) tissue specimens obtained from patients with esophageal cancer. RNA samples were also obtained from over 30 tissue samples. These revealed considerable variation in the abundance of HER-I and c-myc transcripts in both the tumor and adjacent non-tumor specimens. A few samples revealed extremely high levels of these transcripts. Thus, changes in gene copy number or level of expression of HER-I or c-myc DNA sequences may play an important role in the pathogenesis of esophageal cancer in this high-risk region.