It has been increasingly evident that multiple factors are involved in the cause of cancer. We demonstrated previously, DNA sequences related to human T lymphotropic virus type I (HTLV-1) in leukemia and lymphoma as well as carcinoma of certain types in man, and showed that these sequences caused genetic instability of host cells. This study was carried out to examine the possible involvement of HTLV-1 in nasopharyngeal carcinomas (NPC) in which Epstein-Barr virus (EBV) is etiologically implicated, and to discuss potential significance of the involvement. DNA extracted from tumor tissues of 18 patients with NPC was examined for the presence of DNA coding for EBNA-1, LMP-1, HTLV-1-LTR, -gag, and -tax, by PCR-SSCP or PCR-PAGE. EBER-1 and HTLV-I-LPR were examined by in situ hybridization. Serial sections were tested by immunostaining with monoclonal antibody for LMP-1, Ki-67, PCNA, Rb, p53, HER-2/neu, bcl-2, Fas, and BM-1. Positive reactions were seen in 13, 9, 18, 18, 0, 17, 14, 15, 5, 16, 10, 9, and 10 specimens, for EBNA-1, EBER-1, LMP-1, HTLV-I, LMP-1 protein, Ki-67, PCNA, Rb, p53, HER-2/neu, bcl-2, Fas, and BM-1, respectively. Direct sequencing from PCR products of representative cases revealed multiple mutations in HTLV-1-LTR and in bcl-2 sequences analyzed. These results demonstrated the dual involvement of EBY and HTLV-1 in NPC, and deregulation of cellular genes of host cells.