Two species of the Epstein-Barr virus-encoded latent membrane protein 2, LMP2A and LMP2B, are generated by alternative splicing, each species having a distinct first exon. LMP2 transcription in undifferentiated nasopharyngeal carcinoma (NPC), which is consistently associated with the Epstein-Barr virus, was investigated. Fifteen NPC specimens were analyzed by Northern (RNA) blot and RNA-based polymerase chain reaction; the LMP2A transcript was present in all specimens except one. In some specimens the LMP2B transcript was also detected. Sequence analysis of LMP2 cDNAs obtained from two NPC specimens revealed four mutations in exon 1 of the LMP2A transcript, which were present in both tumors and which resulted in nonconservative amino acid changes. These data suggest that the LMP2 expressed in NPC is distinct from that which is expressed in lymphoid cells.