Serum amyloid A protein (SAA) is a precursor for a major component of amyloid fibrils, which, upon deposition, cause secondary amyloidosis in diseases such as rheumatoid arthritis. In mice, SAA is encoded by at least three genes, which show diverse expression during inflammation. Furthermore, in amyloidosis-resistant SJL mice, the gene expression for one SAA isotype, SAA2, is defective, although SAA2 gene expression is normal in amyloidosis-susceptible BALB/c mice. Because only SAA2-derived products deposit in mouse amyloid tissues, the resistance of SJL mice to amyloidosis seems to be due to defective SAA2 gene expression. Thus, the study emphasizes the importance of SAA gene structure in determining susceptibility to amyloidosis.