The effects of EPO on transfusion requirements and HLA allosensitization were studied in a group of 145 sensitized patients on a single cadaveric renal allograft waiting list. All patients included in the study had PRA levels greater than 40% and at least six months of follow-up after the general availability of EPO. A total of 108 (74%) of these patients received EPO during the study period while 37 (26%) did not. The EPO patients had a much higher incidence of prior transfusions than the non-EPO patients (64% vs. 39% P less than 0.05). During the follow-up period, there was a marked reduction in transfusion incidence in the patients who received EPO from 64% to 14% (P less than 0.05). A lesser and nonsignificant reduction in incidence of transfusions was seen in the non-EPO-EPO patients. Analysis of PRA levels in the EPO and non-EPO groups demonstrated a reduction in PRA levels over time but there was no difference between the two groups. When the patients were divided by the need for transfusions in the follow-up period, a comparison of these two groups demonstrated significant differences. At the six-month follow-up point, patients in the nontransfused group had a significantly lower mean PRA than the transfused patients (49% vs. 62%, respectively, P less than 0.05). Furthermore, a greater number of patients in the nontransfused group had PRA declines greater than or equal to 15% compared with the nontransfused group (56/46% vs. 4/15%, respectively; P = .007). Stepwise logistic regression analysis of possible risk factors for persistent high PRA levels demonstrated that continued transfusion was the only significant factor. This study suggests that the institution of EPO therapy in sensitized patients on a single cadaveric waiting list can result in substantial reduction in the need for on-going transfusions. However, the decline in PRA levels appears to be more closely tied to the avoidance of transfusion rather than to the specific institution of EPO therapy.