Undermethylating agents are frequently used in the study of DNA methylation. However, the drugs of choice to induce experimental DNA undermethylation, 5-azacytidine and 5-aza-2'-deoxycytidine, are known to be cytotoxic. We report on S-adenosyl-L-homocysteine (SAH) as an alternative agent for inducing undermethylation of human DNA in vivo. The molecular and cytological evidence presented in this paper clearly suggests that SAH could be even more efficient than the cytidine analogs; in addition, SAH does not exhibit the secondary toxic effects that cripple the usefulness of cytidine analogs.