Red blood cell creatine concentration was examined to determine its association with the equine erythropoietic response. Studies were conducted on 9 healthy horses, 4 healthy ponies, 24 anemia horses, and 2 horses in which anemia was experimentally induced. A modified Jaffe reaction was used to measure RBC creatine concentration. The mean RBC creatine concentration of the 9 healthy horses was 5.72 +/- 0.42 mg/dl, and that of the 4 healthy ponies was 2.59 +/- 0.31 mg/dl. Density-separation of erythrocytes from the healthy horses revealed significantly higher (P less than 0.001) creatine content (7.72 +/- 0.57 mg/dl) in the young RBC populations than in the old RBC populations (4.03 +/- 0.27 mg/dl). The RBC creatine content was assayed in 19 hot-blooded horses which were anemic due to a variety of causes. Of these anemic horses, 12 with PCV between 25% and 30% had a mean RBC creatine concentration of 6.12 +/- 0.46 mg/dl. The 7 other anemic horses with PCV less than 25% had a mean RBC creatine value of 6.07 +/- 0.12 mg/dl. Bone marrow films were examined from 5 anemic horses and in the 2 horses in which anemia was experimentally induced. The RBC creatine concentration correlated positively (P less than 0.001) with the reticulocyte count in the bone marrow and negatively with the myeloid-erythroid ratio (P less than 0.001).