The structure and expression of the gene encoding serum amyloid P (SAP) component of the Syrian hamster have been studied by isolation of cosmid clones, nucleotide sequence analyses, and quantitation of nuclear run-on transcripts, nuclear RNA, mRNA, and protein levels. Hamster SAP, originally identified as female protein (FP), is a unique pentraxin because pretranslational expression of this gene is modulated by mediators of inflammation and sex steroids. SAP(FP) levels are high in sera from female hamsters and low in males. The response to inflammation is divergent; SAP(FP) levels decrease in females and increase in males during an acute phase response. The SAP(FP) gene encodes a 211 amino acid residue mature polypeptide as well as a 22-residue signal peptide. The intron/exon organization is similar to that of other pentraxins, but additional transcripts are generated from alternate polyadenylation sites in the 3' region. Circulating levels of SAP(FP) and the corresponding hepatic transcript levels are augmented by estrogen, while testosterone, dexamethasone, and progesterone cause a decrease in these levels. In addition the cytokines interleukin-1, -6, and tumor necrosis factor mediate a decrease in hepatic SAP(FP) transcript levels in female hamsters but did not cause a significant elevation of SAP(FP) mRNA in livers of male hamsters. The differences in expression of the SAP(FP) gene between male and female hamsters between unstimulated male hamsters and male hamsters stimulated with an injection of lipopolysaccharide are due, at least in part, to alterations in transcription.