Telomerase activity is found in the majority of human cancers, but not in most normal tissues. It is generally accepted that there is a multistep process in human carcinogenesis. Studying the role of telomerase activation in this process may provide new information to further our understanding of the pathological process of clinical lesions. In the present study, telomerase activity was found in HPV-immortalized and cigarette smoke condensate (CSC)-transformed malignant cell lines established in a cervical carcinogenesis model and in cell lines derived from cervical intraepithelial neoplasias (CINs) and carcinomas. With exfoliated cell samples, telomerase activity was detected in 3 of 41 (7%) normal cervices, 10 of 25 (40%) CINs, and all 20 (100%) carcinomas. Telomerase activation was significantly higher in CINs than in normal cervices (chi2 = 7.42, P < 0.01) and was much higher in invasive carcinomas than in CINs (chi2 = 18.00, P < 0.005). Our observations suggest that telomerase activation is a relatively early-stage event in cervical carcinogenesis, and this activation is associated with the initiation and progression of cervical lesions. Detection of telomerase activity may serve as a tool for diagnosis and prognosis of cervical neoplasias.