Background. We examined whether deoxyspergualin (DSG) prophylaxis in combination with cyclosporine (CsA)- or tacrolimus (Tac)-based immunosuppression augments the effect of donor-specific blood transfusions (DSTs) to improve long-term survival of living-related renal-transplants. Methods. From May 1985 to January 1998, 176 patients received DST from one-haplotype-identical donors prior to kidney transplantation. Group A (n = 64, 1985 to 1989) received CsA, prednisolone (PSL), antilymphocyte globulin (ALG), and azathioprine (AZA). Group B (n = 89,1989 to 1996) received CsA, PSL, ALG, and DSG. Group C (n = 23,1996 to 1998) received Tac, PSL, ALG, and DSG, with DSG followed by AZA. Rejection episodes were classified as acute rejection (AR, within the first 3 months) or late acute rejection (LAR, from 4 months to 1 year). Results. Five-year graft survivals were 73.4%, 88.8%, and 91.3% for groups A, B, and C, respectively. The incidence of AR was 34%, 30%, and 13%, and that of LAR was 23%, 26%, and 30% for groups A, B, and C, respectively. There was no significant difference in the incidence of AR or LAR among the three groups. However, an elevated serum creatinine (sCr) >= 1 mg/dL was observed in 73%, 15%, and 0% of patients during AR, and in 53%, 30%, and 14% during LAR for groups A, B, and C, respectively. These results suggest that the severity of AR or LAR was lowest among group C, contributing to the improved long-term graft survival in these patients. Conclusions. DSG prophylaxis with Tac-based immunosuppression further improves long-term graft survival among living-related renal-transplant recipients treated with DST by decreasing the severity of acute rejection episodes.