The current work presents the investigation on IFN-α/β expression in rat liver after partial hepatectomy (PHE) and laparotomy (LAP). These operations were used to model the regeneration process and the acute phase response as a component of regeneration process. The relative content of IFN-α in total liver cytosol and IFN-α- and IFN-β-specific RNAs in total liver RNA were assessed by the biological test and by reverse transcription-polymerase chain reaction, respectively. IFN-α-specific RNA and IFN-α protein were shown to be expressed in the intact and regenerating liver. IFN-β-specific RNA is not detected. IFN-α delivery to the liver via blood from other INFα - producing cells is highly unlikely due to its negligible concentration in the blood serum. PHE induces the increase of IFN-α-specific RNA and protein content during G0/G1 transition of the liver from quiescence to proliferation (1-3 hours after PHE) with the further decrease in their content towards the G1/S transition of hepatocytes (12 hours after PHE). Quantitatively the up-regulation of IFN-α expression was less than maximally possible, which was observed after injection of typical inducer of IFN-a synthesis, poly(I)-poly(C). LAP completely blocked IFN-α expression which was manifested at RNA and protein level in 1, 3, 6, and 12 hours after the operation. Thus, the increase in IFN-α expression at the early phase of regeneration is essential for liver transition from quiescence to proliferation and IFN-α expression is incompatible with the acute phase response. A role of IFN-α in both processes is yet to be defined. The decrease in IFN-α expression till the G1/S transition of hepatocytes in 12 hours is consistent with a widely known concept about antiproliferative activity of IFN-α.