Serum amyloid A (SAA) is highly induced during many inflammatory episodes. The induction mechanism in response to turpentine and lipopolysaccharide (LPS), two major inducers of this gene, was investigated. Here we present evidence that although both agents triggered expression, SAA mRNA synthesized in the turpentine-injected rabbit liver is many-fold higher compared to that found in LPS-injected rabbit liver. We demonstrate that differential level of activation of C/EBP and NF-κB that interact with the proximal promoter of SAA gene is responsible for the differential expression. A very high level of C/EBP induction with little or no activation of NF-κB factors was noted when turpentine was used as the inducer. LPS, on the other hand, activated NF-κB and C/EBP, which were detected only at the early phase of induction process. These results indicate that different pathways might be activated for the regulation of hepatic expression of SAA by different inflammatory agents. One of the pathways, triggered by LPS, requires participation of both NF-κB and C/EBP. A second pathway, triggered by turpentine, involves only C/EBP family of transcription fact