The effect of pretransplant donor-specific blood transfusions on the survival of subsequent skin allografts was studied in adult congenic B10 mice disparate at various regions of the H-2 complex. Donor-host combinations were used that were disparate either at isolated K or I regions or at combined K/D and I regions. Recipient mice were given a single donor-specific blood transfusion ten days before antilymphocyte serum (ALS)4 treatment and skin grafting. A beneficial effect of donor-specific blood transfusions on skin graft survival was observed only in donor-recipient combinations that differed at the K and I regions. Disparity at the IA and IJ subregions appeared to be particularly important in obtaining the transfusion effect. Donor-specific transfusion had no effect on graft survival in donors and recipients disparate at only the K region, the D region plus part of the I region, or the entire H-2 complex. Pregraft transfusion in mice disparate at the I region sensitized the recipients to subsequent skin grafts from the blood donor. These results indicate that both antibody and suppressor cells play a role in the induction of the beneficial effect obtained from pretransplant donor specific transfusions.