Young rats were maintained in a 10% oxygen atmosphere for 2, 6, and 10 days and administered normal rat chow and water ad libitum. Thereafter, their hepatic S‐adenosyl‐L‐methionine (AdoMet) and activity and mRNA levels of AdoMet synthetase were assayed. AdoMet levels decreased by 45% after 10 days; hepatic AdoMet synthetase also declined by ∼40%. In rats with low hepatic AdoMet, the mRNA level of AdoMet synthetase also declined by up to 80%. No significant change in AdoMet or AdoMet synthetase was noted in pair‐fed normoxic rats. DNA hypomethylation was determined in terms of incorporation of [³H]methyl of AdoMet incorporated at unmethylated sites in DNA in reactions mediated by methylases Hpall and Sssl. As compared to the normal hepatic DNA, [³H]methyl group incorporation in the 10‐day hypoxic DNA was almost double in the Hpall‐mediated reaction and ∼10‐fold in the Sssl‐mediated reaction. Hepatic tRNA methyltransferase activity doubled after 10 days of hypoxia. However, hypoxic rats showed no detectable mRNA transcripts for c‐myc and c‐fos oncogenes on Northern blot analysis. These observations show that because of subnormal activity of AdoMet synthetase, hypoxic liver is depleted of AdoMet, even when the animals are administered a complete diet. However, unlike rats on chronic lipotrope‐deficient diets, hypoxic rats on a complete diet show no aberrant expression of oncogenes. © 1996 Wiley‐Liss, Inc.