It has been hypothesized that infection with high-risk human papillomaviruses (HPVs), in conjunction with other cellular events, plays a critical role in the development of cervical cancer. Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, has been associated with acquisition of the immortal phenotype in vitro and is commonly observed in human cancers. In this study, we have examined 10 high-grade cervical cancers for telomerase activity and for the presence of HPV. Telomerase activity was detected in all of the cancers but in none of the paired histopathologically normal uterine tissues or in normal cervical epithelium. Analysis of these same tissues for HPV nucleic acids by polymerase chain reaction (PCR) using primers from the HPV L1 and E6 open reading frames demonstrated that 7 of 10 cancers were positive for HPV, 3 for HPV type 16 (HPV-16), and 4 for HPV-18. In one case, HPV-16 was detected in histopathologically normal uterine tissue, the same type as that detected in the cancer from the same patient. HPV DNA was not detected in 3 of 10 cancers. These results indicate that telomerase activation is common in high-grade cervical cancers and suggests that telomerase activity may be a useful diagnostic marker for the disease.