The study was aimed at determining the effects of longterm administration to rats of aspirin or acetaminophen (ACAP) on liver folate content and distribution as well as whether or not hepatocyte DNA was methylated at the end of the treatments. In addition, S-adenosylmethionine and S-adenosylhomocysteine hepatic concentrations were determined. In liver, aspirin or ACAP administration were not associated with important changes in total folate content or glutamic acid chain length distribution. DNA methylation assessed by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using (3H-methyl)S-Ado Met as methyl donor, resulted in similar [3H] methyl incorporation into DNA regardless of the drug. The long-term administration of the analgesics did not result in significant changes in S-AdoMet/S-AdoHcy ratios.