The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis. This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated. After 16 hours, livers were perfused in situ, and bile flow, synthesis rates of albumin and alpha 1-acid glycoprotein (a major acute-phase protein in rats), and release of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) into perfusate were determined. Within the same livers, sepsis resulted in a 54% increase in the synthesis of alpha 1-acid glycoprotein and approximately 30% inhibition of albumin synthesis concomitant with 50% lower bile flow. The concentrations of GOT and GPT in the perfusate increased slightly during the experiments, both when control and septic livers were perfused. The maintained tissue levels of adenosine triphosphate (ATP) and the uptake of Evans blue dye by less than 1% of the hepatocytes, although a late test of viability, suggest that both control and septic livers remained viable during perfusion. The results are consistent with the concept that different hepatocellular functions are individually regulated during sepsis. Thus, impairment of certain hepatocellular functions does not necessarily imply generalized liver failure.