The regulation of the synthesis of plasma proteins in rat liver during the acute phase response was studied by measuring gene transcription activities in a cell-free nuclear transcription system. The transcription activities for the genes of major acute phase alpha 1-protein, the beta-chain of fibrinogen, transferrin, alpha 1-acid glycoprotein, and alpha 2-macroglobulin increased, reaching a maximum level between 18 and 36 h after inducing an acute inflammation. The transcription activities for the genes of alpha 2u-globulin, albumin, and transthyretin (formerly called prealbumin) decreased, reaching a minimum level after 12 to 24 h. The extent of the relative changes in transcription activities was similar to that of the relative changes in mRNA levels for major acute phase alpha 1-protein, the beta-chain of fibrinogen, transferrin, alpha 2u-globulin, albumin, and transthyretin. This is consistent with the assumption that the principal mechanism of the regulation of the synthesis of these proteins operates at the level of transcription. In contrast, the relative changes in transcription activities for alpha 1-acid glycoprotein and alpha 2-macroglobulin were far smaller than the changes of their mRNA levels, suggesting that, in addition to transcriptional changes, other mechanism(s) are involved in the regulation of the synthesis of these proteins.