The origin of SL family mice was studied by analyzing 100 microsatellite loci, the major histocompatibility complex, the Mx gene, murine leukemia provirus, and mammary tumor provirus. From the genetic profile of family members and their history, we assumed the existence of a proto-SL mouse, an ancestor of all SL family members. Many alleles were contributed to the proto-SL by the ancestors related to strains A2G and CF#1, and/or some wild mice. Among four existing family members, SL/Am and SL/Ni mice were almost identical and presumably closest to the proto-SL. The SL/Kh mouse was derived from a cross of the proto-SL and AKR mice, because SL/Kh mice inherited a considerable number of genes from AKR mice, the most outstanding of which were those of the provirus Emv-11 and Thy-1.1. The SL/QDj mice seemed to be a recombinant inbred strain between SL/Am and SL/Kh mice, because their alleles at all 100 microsatellite loci were shared by SL/Am or SL/Kh strains or both. All four SL family members shared the major histocompatibility complex haplotype q.