Objective: The purpose of this study was to examine telomerase activity and apoptotic changes in HeLa cells persistently infected with influenza viruses B/Lee/40 (He/Le cells). Methods: He/Le cells were established as described previously [Intervirology 2002;45:67–70], and passaged twice a week. The existence of influenza virus genes was monitored by the reverse transcription polymerase chain reaction (RT-PCR). Telomerase activities in He/Le cells were assayed by Telochaser (stretch PCR method). Apoptotic changes in He/Le cells were examined using the Apoptotic DNA Ladder Kit and the In situ Cell Death Detection Kit, Fluorescence. Results: In He/Le cells, (1) all eight influenza virus genes were detected by RT-PCR until 62 days post infection (p.i.); (2) only nucleoprotein gene remained detectable until 120 days p.i.; (3) telomerase activity of He/Le cells normalized to those of uninfected HeLa cells was remarkably decreased (16–55% of control) during the persistence of influenza and recovered up to 80% of control on day 168 p.i. when no influenza virus gene was detected by RT-PCR, and (4) no apoptotic changes were detected despite the continuous existence of influenza virus genes. Conclusion: In He/Le cells, telomerase activity was suppressed exclusively during the persistence of influenza, and no apoptotic changes were detected.