The role of Kupffer cells (KC) in the induction of tolerance caused by preoperative donor-specific blood transfusion (DST) was investigated. DA rats (RT1^a) were used as donors and Lewis rats (RT1^l) as recipients. Recipients of an orthotopic liver transplantation (OLT) were divided into eight groups: Group 1, only OLT was performed; Group 2, on Days 9 and 8 before OLT, gadolinium (Gd) was injected intravenously; Group 3, on Day 7 before OLT, donor blood was injected intravenously (ivDST); Group 4, DST was performed via the portal vein (ipvDST); Group 5, Gd was injected twice as described for Group 2 before ivDST; Group 6, Gd was injected as described for Group 2 before ipvDST; Group 7; ivDST was performed, and then on Days 3 and 2 before OLT, Gd was injected; Group 8, ipvDST was performed, and then Gd was injected as described for Group 7. The mean survival times (MSTs) were 11.6, 11.8, 52.7, 64.4, 27.7, 39.4, 49.4, and 64.2 days in each group. That is, injection of Gd only or injection after DST had no effects for the survival days of recipients. There was no statistically significant difference between Group 6 and Groups 3 and 4, but the MST of Group 5 was significantly shorter than those of Groups 3 and 4. Microscopic studies demonstrated marked portal and lobular infiltration and endothelialitis, as well as necrosis of the parenchyma and paucity of interlobular bile ducts in Groups 1, 2, and 5. While in Groups 3, 4, and 6 these findings were considerably mild. These results suggested that KC participated in the induction of tolerance caused by DST and that portal venous injection of donor blood diminished the effects of Gd.[ep[rs