Zenapax (Daclizumab) is a novel immunosuppressive agent, which has been shown to promote allograft outcome in low-risk renal allograft recipients. However, its efficacy on high-risk recipients has not yet been established. We conducted a prospective randomized clinical trial to evaluate the effect of Zenapax induction therapy compared with ALG in high-risk recipients, from 2000 to 2002. Twenty five re-transplanted patients as high-risk recipients were randomized into two groups. Group 1 (n=11) received Zenapax prophylaxis (1 mg/kg pre-operatively and at days 14, 28, 42, 56 after operation). Group 2 (n=14) received ALG prophylaxis (10 mg/kg pre-operatively continued for 10 to 14 days after operation). Baseline immunosuppression consisted of Cyclosporine, Prednisolone and Mycophenolate mofetil. Recipients' sex, age, etiology of ESRD, PRA serostatus, as well as donors' sex and age were comparable between two groups. All patients received re-transplantation from unrelated living donors. Acute rejection was observed in 8 and 2 patients of ALG and Zenapax groups, respectively (P= 0.04). There was no difference regarding to rate of ATN between two groups. No graft loss was seen in Zenapax group, whereas there were 4 graft failures in ALG group. One-year graft survival was 100% in Zenapax group vs. 68.7% in ALG group (P=0.05). Occurrence of complications due to bone marrow suppression was significantly lower in Zenapax group. Anemia occurred in one patient in Zenapax group vs. five patients in ALG group (P=0.04). Five cases of leukopenia and four thrombocytopenia were observed in ALG group whereas none patients in Zenapax group experienced these two complications (P=0.007 and P= 0.02, respectively). Rate of CMV infection was similar in two groups. In conclusion, this study suggested that Zenapax prophylaxis yielded lower complications as well as was more easily used compared with ALG. In addition, it seems Zenapax can improve graft outcome and reduces incidence of the acute rejection episodes in high-risk kidney recipients.