We have presented some data from studies of two different DNA cytosine methyltransferases. The first enzyme, M. Hha I, was shown to catalyze 3H exchange from poly (dG.[5-3H] dC), at a rate that is 7 to 10 times greater than the rate of methylation. The exchange is inhibited by AdoHcy in an uncompetitive fashion. This pattern of inhibition suggests an ordered reaction sequence for M. Hha I catalyzed methylation. The second enzyme, M. Hpa II, was demonstrated to make an irreversible adduct with azaC-DNA. The results provide evidence that both enzymes form covalent dihydropyrimidine intermediates during catalysis.