Improvement in erythropoiesis following renal transplantation (RT) was assessed in 74 consecutive patients by serial measurements of serum erythropoietin (EPO), hematocrit, absolute reticulocyte count (ARC) and serum creatinine during the first month after RT. The reticulocyte maturity index (RMI) which provides an objective measure of red-cell maturity was assessed in 31 patients by flow cytometry using thiazole orange. In group I (n = 39) with immediate graft function, EPO levels increased rapidly from day 2 and remained elevated at the plateau between two and three times the upper limit of normal during the first 2 months. In group II (n = 29) with delayed graft function, EPO levels increased gradually from day 10 when renal function improved significantly. No particular significant biphasic pattern of secretion was detected in group I or II. In both groups, hematocrit rose to over 35% approximately 3 months after RT. In a third group (n = 6) with immediate postoperative acute blood loss and severe anemia, a hematocrit fall was followed by a steep increase in EPO levels with a negative correlation between hematocrit and EPO levels during the first 4 days. During acute rejection, EPO diminished significantly by more than 50% either on the day of diagnosis or on the following days in 8 patients. RMI increased by 25% over the pretransplantation values by 7 days on average before the ARC rose. Thus the RMI seems to be an early sensitive predictor of erythropoiesis after RT. EPO response after RT depends on graft function, and the early transient increase in EPO observed in patients with acute blood loss may explain the apparent biphasic response previously reported.