In vivo an acute phase reaction is characterized by changes in hepatic protein metabolism and modification of liver drug enzymes (cytochrome P-450). In vitro, mediators of an acute phase reaction have been reported to have a similar effect. In the present study, the effects of bacterial endotoxin (lipopolysaccharide, LPS) and cytokines in hepatocyte cultures of rat and hamster were examined. In both species, a significant increase in secretion of specific acute phase protein was measured after 48 hr of exposure to IL-6, TNF-alpha or LPS. LPS and TNF-alpha increased the secretion of serum amyloid A (SAA) in hamster hepatocytes. LPS and IL-6 (but only in the presence of hydrocortisone) increased the secretion of alpha2-macroglobulin (alpha2M) in rat hepatocytes. An effect on the total concentration of cytochrome P-450 was not found in either species after exposure to glucocorticoids or to LPS and cytokines, although the latter compounds caused a marked increase in secretion of acute phase proteins.