OBJECTIVE The objective was to study the relationship between the tumor factor of cancer MATLT and the catalytic subunit of telomerase. The function of telomerase in the blockade of cell differentiation and in the protection of DNA MT resembles closely the function of the tumor factor of cancer MATLT. Because of this close similarity we made an attempt to examine the possibility that the tumor factor of MATLT might be the catalytic subunit of telomerase. METHODS We used purified MAT isozymes, telomerase antibody, immunoprecipitation, and a selective inhibitor of the tumor factor of MATLT from urine to study the relationship between the tumor factor of MATLT and telomerase. RESULTS We were able to show that the tumor MATLT, but not the liver MATL, was selectively inhibited by the telomerase antibody, and the tumor MATLT, but not the liver MATL, was preferentially immunoprecipitated with the telomerase antibody. The catalytic subunit of telomerase was detectable in the tumor MATLT preparation by immunoblotting, but was undetectable in the liver MATL preparation and the tumor MATL preparation stripped o. Of the tumor factor. In addition, PP-0.39, which is an effective differentiation inducer purified from urine previously found to selectively antagonize the tumor factor of MATLT, was found in this study to be a potent inhibitor of telomerase. The inhibition of telomerase by PP-0.39 was far more sensitive than the elimination of the tumor factor from MATLT. CONCLUSION All results are consistent with the hypothesis that the tumor factor of MATLT is the catalytic subunit of telomerase. Thus, the blockade of cell differentiation by telomerase is mediated through its interaction with MAT to affect methylation enzymes, so that hypomethylation of nucleic acids necessary for the cell to undergo differentiation cannot take place.