Telomerase activity is found in most cancer tissues and many immortalized cell lines as well as in germ line cells but it is generally undetected in normal human somatic tissues. There is weak telomerase activity in some cell types of hematopoietic lineage in which a stem cell-like subpopulation may exist. Likewise, physiologically regenerating somatic tissues and organs such as skin, small intestine, and most other epithelia of the human body are supposed to contain similar cell lineages to maintain their renewal throughout the life span of individuals. It is therefore of interest whether telomerase activity is present in physiologically regenerating epithelial cells. Telomerase activity was detected, though very weakly, in cultured normal epidermal keratinocytes and at higher levels in a subpopulation that adhere rapidly on collagen IV-coated culture dishes. No telomerase activity was detected in a subpopulation that was less adherent on the coated dishes. The rapidly adherent subpopulation of keratinocytes was enriched in small proliferating cells with macrocolony forming potential. It was also passaged through more generations in culture, and expressed integrin beta 1 at higher levels than the less adherent subpopulation. Telomerase activity was similarly found in ectocervical keratinocytes as well as in simple endocervical epithelial cells. These findings provide the evidence of a telomerase-positive population among physiologically regenerating normal human epithelial cells. The identity of the telomerase-positive cells remains to be defined.