Background: Ly-6A/E, also known as Sca-1, is an 18 kD member of the Ly-6 multigene family. Ly6A/E is a glycosylphosphatidylinositol (GPI)-linked protein expressed on hematopoietic stem cells. In mice expressing the Ly-6.2 haplotype (e.g., AKR, C57BL, C57BR, DBA/2, SJL, SWR, and 129), Ly-6A/E is also expressed on peripheral B lymphocytes and thymic and peripheral T lymphocytes. Strains expressing the Ly-6.1 haplotype (e.g., BALB/c, CBA, C3H/He, DBA/1, and NZB) have low Ly-6A/E expression on resting peripheral lymphocytes. The expression of Ly-6A/E on lymphocytes is upregulated upon activation from both Ly6.1 and Ly6.2 haplotype mice. Ly-6A/E is thought to be involved in the regulation of both T and B cell responses.