Immunological enhancement of allogeneic heart graft survival by serum from rats tolerized by liver grafting has been studied. Serum taken from long-term-surviving PVG rats carrying orthotopic DA liver transplants (OLT serum) was able to increase the survival time of PVG.RT1a heterotopic heart grafts in PVG recipients. Administration of 1 ml of OLT serum at the time of heart grafting led to permanent survival of the grafts in all animals. The recipients became systemically tolerant of RT1a and several weeks later were able to accept permanently skin grafts from the same donor strain, while rejecting third-party grafts. Enhancement appeared to be mediated initially by IgG antibodies in the OLT serum against class II donor RT1a antigens; significant enhancement was produced by as little as 100 micrograms of antibody. Recipient alloantibody responses following enhancement were studied and showed selective suppression of the anti-class-I (RT1Aa) antibody levels, while the anti-class-II antibody response was apparently unaffected. The implications of these results for mechanisms of unresponsiveness following enhancement and liver transplantation are discussed.