1. DNA-methylase activity from Escherichia coli strains KB, B and W and from Azotobacter was tested using DNA acceptors from bacteria, mouse organs and tumors, and polyoma virus. DNA substrates could be distinguished with regard to species and strain specificity by their rate and extent of methylation and by the ratio of incorporation into 5-methylcytosine as compared with 6-methylaminopurine. Under the same conditions, DNA samples from normal mouse organs and from mouse tumors showed no significant differences when methylated by bacterial DNA methylases. 2. Polyoma virus DNA was enzymically methylated in vitro, and tested for infectivity. It showed the same plaque-forming ability as the normally occurring non-methylated polyoma DNA. 3. Heparin (as well as polylysine) was found to inhibit nucleic acid methylase activity when present at a final concentration of 1 μM or greater. 4. Ethylation of DNA was observed using S-adenosyl [ Et- 14C]ethionine as a source of ethyl groups.