Since multistage carcinogenesis is frequently associated with the loss of suppressor gene activity, and since in over 90% of cases of nasopharyngeal carcinoma (NPC) p53 alterations are not involved [Sun, Y., Hegamyer, G.H., Cheng, Y.-J., Hildesheim, A., Chen, J.-Y., Chen, I.-H., Cao, Y., Yao, K.-T. & Colburn, N.H. (1992). Proc. Natl. Acad. Sci. USA, 89, 6516-6520] we investigated the possible involvement of the inactivation of the retinoblastoma susceptibility gene (RB) in nasopharyngeal carcinogenesis. We analysed the expression, gross structure and possible point mutation of the RB gene in an NPC cell line as well as seven NPC biopsies obtained from seven patients. The NPC cell line expresses the RB gene with a normal size and abundance, as assayed by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern hybridization. No point mutation was detected in two independent E1A/large T-binding regions, which are the common sites for mutations in the RB gene. NPC biopsies also showed no point mutations at four exon-intron boundaries at which point mutations have been reported in other human carcinomas. The biopsies and cell line had no deletions in the promoter region of the gene and showed no gross deletions or rearrangements. Taken together, we conclude that, in contrast to multistage carcinogenesis leading to human retinoblastoma, osteogenic sarcomas and carcinomas of lung, breast, bladder and prostate, nasopharyngeal carcinogenesis appears unlikely to involve RB gene alterations.