Objective: To investigate whether donor-specific tolerance can be induced in adult rats with intact immune system. Methods: Adult BN and DA rats were used as donors and Lewis rats as recipients. Donor rats were treated with dexamethasone (DEX) intraperitoneally either prior to their splenectomy or prior to heart procurement. The recipients either received spleen cell transfusion from DEX-treated donors (DEX-SPC) 2 weeks before cardiac transplantation, or directly underwent cardiac transplantation with grafts from DEX-treated donors (DEX-GRAFT), or received combined treatment of both (DEX-SPC+DEX-GRAFT). In one group the recipients were also treated with DEX before DEX-SPC transfusion and perioperatively. Results: Significant donor-specific prolongation of graft survival was observed in DEX-SPC group and even longer graft survival found in recipients with combined treatment of DEX-SPC and DEXGRAFT. However, when the recipients with combined treatment were treated with DEX before and after transfusion and perioperatively (DEX-SPC+DEX-GRAFT+Recipient-DEX), the graft survival was decreased. Conclusion: Donor-specific tolerance can be induced in immunologically intact adult animals by intravenousdonor lymphocyte transfusion, indicating that tolerance or rejection of an antigen may not be decided by the self or non-self nature of the antigen or by the developmental stages of the recipients, but can be very likely to be related to the down-regulation of dendritic cell number or function that result in failure of supplying costimulation signals.