Telomeres ofPhysarumplasmodia did not shorten with numerous repeats of nuclear division, and an apparent activity of telomerase was detected in this organism. In naturally synchronized culture ofPhysarumplasmodia, an evident activation of telomerase was observed at the late S-phase, just prior to the completion ofin vivoDNA replication, and the low telomerase activity was detected throughout the cell cycle. In the nuclei isolated from different phases of synchronized plasmodia, a higher activity of telomerase was also observed at late S-phase. These results clearly show the existence of a cell cycle-dependent regulatory mechanism of telomerase activity in growing, naturally synchronized cells.