Trophoblasts are derived from the normal placenta, and they infiltrate into the endometrium and the maternal blood vessels under strict control but, unlike malignant cells, never metastasize. To understand the proliferative characteristics of trophoblasts and its related disorders, we assessed telomerase activity in chorionic villi obtained from 27 normal individuals, 9 hydatidiform moles, and 2 choriocarcinomas. Telomerase activity was detected in 13/27 (48%) normal chorionic villi samples. The detectability and the level of telomerase activity depended on gestational age; 8/10 (80%) villi samples in the first trimester (relative telomerase activity; 1.77 +/- 1.37), whereas 2/8 (25%) villi samples in the second trimester (0.78 +/- 1.52) and 3/9 (33%) in the third trimester (0.28 +/- 0.43) had telomerase activity. Telomerase activity of normal chorionic villi in the first trimester was higher than that of the third trimester (P = 0.0251). In contrast, all mole samples had increased telomerase activity compared to normal villi (3.17 +/- 2.81, P = 0.0152). Thus, a relationship may exist among cell proliferation, telomerase activity, and progression to trophoblastic disease.