A large number of genetically defined, isogenic strains of domestic Syrian hamsters (BIO) have been studied for their immunogenetic relationship to the inbred hamster strains MHA and CB, and to a partially inbred, recently wild strain, MIT. The results indicate that all BIO strains are histoincompatible with the inbred and recently wild strains maintained in our colony. They reject exchanged skin allografts, their lymphocytes participate in vigorous mutual mixed lymphocyte reactions. Moreover, transplantation alloantigens have been identified by serological testing with antisera recently developed by immunizing inbred hamsters with tissue from recently wild animals and vice versa. However, the incompatibility is strongest with the CB and MIT strains. Individual hamsters from many of the BIO strains accept MHA skin grafts indefinitely, fail to respond to MHA cells in mixed lymphocyte reactions, and type serologically as identical to MHA. We concluded that there must have been very little alloantigenic variation present among the three littermate hamsters caught in 1930 from which the local inbred and BIO lines are derived. Moreover, after 40 years there has been little, if any, mutational change in this restricted gene pool, at least as it can be expressed in histocompatibility assays. These findings address the issue of the extent of alloantigenic diversity among Syrian hamsters.