Gene expression profiling was carried out comparing Con A elicited peritoneal macrophages from C57BL/6 and FVB/N wild-type and apolipoprotein (apo)E knockout mice. An EST, W20829, was expressed at higher levels in C57BL/6 compared with FVB/N mice. W20829 mapped to an atherosclerosis susceptibility locus on chromosome 19 revealed in an intercross between atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant FVB/N apoE knockout mice. A combination of database search and Northern analysis confirmed that W20829 corresponded to 3′-UTR of a hitherto predicted gene, named HspA12A. Blasting the National Center for Biotechnology Information database revealed a closely related homologue, HspA12B. HspA12A and -B have very close human homologues. TaqMan analysis confirmed the increased HspA12A expression (2.6-fold) in elicited peritoneal macrophages from C57BL/6 compared with FVB/N mice. TaqMan analysis also revealed increased HspA12A and HspA12B expression (87- and 6-fold, respectively) in lesional versus nonlesional portions of the thoracic aorta from C57BL/6 apoE knockout mice on a chow diet. In situ hybridization confirmed that both genes were expressed within lesions but not within nonlesional aortic tissue. Blasting of HspA12A and HspA12B against the National Center for Biotechnology Information database (NR) revealed a hit with the Conserved Domain database for Hsp70 (pfam00012.5, Hsp70). Both genes appear to contain an atypical Hsp70 ATPase domain. The BLAST search also revealed that both genes were more similar to primitive eukaryote and prokaryote than mammalian Hsp70s, making these two genes distant members of the mammalian Hsp70 family. In summary, we describe two genes that code for a subfamily of Hsp70 proteins that may be involved in atherosclerosis susceptibility.