We studied mitochondrial DNA (mtDNA) replication and transcription in association with major hepatectomy. Changes in nuclear respiratory factor 1 (NRF-1) mRNA and RNA moiety of mitochondrial RNA-processing endoribonuclease (MRP-RNase RNA) were followed at 0, 3, 6, 12, and 24 h after hepatectomy. Contents of mtDNA, cytochrome b mRNA, and beta-actin mRNA were also measured. Contents of NRF-1 mRNA and MRP-RNase RNA increased to maximum or sub-maximum level 1 h after hepatectomy. mtDNA and cytochrome b mRNA increased to maximum level 3 h after. On the contrary, content of beta-actin mRNA increased to maximum level 12 h after. From these results, mtDNA replication and transcription occurred in the initial phase of liver regeneration, which might lead to an increase in mitochondrial respiratory function in the remnant liver, and cytoskeleton proteins such as beta-actin were followed thereafter.