Serum amyloid P (SAP), a phylogenetically conserved pentraxin, is an integral component of all amyloid deposits. Regulation of expression of SAP gene expression is quite different in two related hamster species. In Syrian hamsters, the resting serum levels of SAP are determined by gender, and the direction of alteration following inflammation is divergent. In Armenian hamsters, SAP is not a prominent acute-phase reactant and there is no gender dimorphism of expression. The structure and expression of the SAP gene of the Armenian hamsters was investigated by isolation of genomic clones, nucleotide sequence analysis, and RNA studies. The gene structure of Armenian hamster SAP is similar to the genes of all other pentraxins studied. While the upstream regions of the SAP genes of Syrian and Armenian hamsters are quite similar, important differences in potential enhancer sites have recognized by comparing the corresponding sequences of SAP genes from both species. Little alteration in hepatic levels of transcripts encoding SAP or CRP, the other pentraxin, were noted following administration of lipopolysaccharide to Armenian hamsters. This relative lack of response occurred despite a marked acute phase reaction documented for serum amyloid A mRNA levels.