The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was synthesized when the system contained CRF sera (total series, p = 0.0001). There was no evidence of inhibition of heme synthesis by serum from 12 patients with the anemia of chronic diseases (CD). Mixing experiments with normal and CRF sera suggested that this defect in CRF serum was not due to lack of a factor necessary for heme synthesis. Addition of urea, creatinine, and guanidinosuccinic acid to normal serum did not impair its ability to support erythropoiesis in this system. These data demonstrated that serum from patients with CRF contains a material inhibiting erythropoiesis in vitro, We propose that the material is responsible, in part, for the clinically severe anemia seen in these patients.

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