Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are products of two genes (MAT1A and MAT2A, respectively) that catalyze the formation of S-adenosylmethionine (SAM), the principal methyl donor. We previously showed that MAT2A expression was associated with more rapid cell growth. Here we examined changes in hepatic MAT gene expression and related consequences after two-thirds partial hepatectomy (PH) in rats. The mRNA levels of both MAT forms increased from 3 to 6 h, but the MAT1A level then fell below baseline from 12 to 24 h, whereas the MAT2A level remained elevated up to 4 days after PH. The increase in the MAT2A mRNA level was due to increased gene transcription and mRNA stabilization. The change in the MAT1A mRNA level was posttranscriptional and did not require de novo protein synthesis. Changes in MAT activity were consistent with an increased amount of MAT isozymes. SAM levels, the ratio of SAM to S-adenosylhomocysteine (SAH), and DNA methylation fell from 6 to 24 h, whereas SAH levels increased slightly at 12 and 24 h after PH. Both increased SAM utilization and MAT2A gene expression likely contributed to the fall in SAM.