We detected telomerase activity in human lymphocytes obtained from normal donors. Telomerase was up-regulated within 24 h when peripheral blood mononuclear cells were cultured in the presence of phytohemagglutinin. The activity increased gradually over 72 h, then remained stable for 96 h. During this period, cell number and the length of telomeric DNA remained constant. Anti-CD3 monoclonal antibody and Pansolbin also induced telomerase activity. These results demonstrate that telomerase is regulated during lymphocyte activation as cells progress from G0 to S phase. This system is useful for the study of telomerase during carcinogenesis, and in the testing of telomerase-inhibitory drugs.