Patients with chronic renal disease in whom erythropoietin production is inadequate invariably experience moderate to severe debilitation-induced fatigue. Unlike the direct humeral control of erythropoiesis, neutropenia in the same cohort of patients appears to be under indirect control, very likely brought about by the suppressive effect of increased levels of low-density lipoprotein (LDL) on granulocyte-monocyte colony formation. Markedly elevated LDL levels were identified in plasma samples obtained from a study population of 179 chronic renal disease patients. The effect of the elevated LDL levels in the plasma of these patients resulted in a >60% decrease in granulocyte-macrophage colony-forming unit in comparison with age-matched plasma from normal individuals. Careful review of all nutritional and therapeutic events in these patients did not offer any evidence, other than the elevated LDL levels, in support of the etiology of the chronically low absolute neutrophil counts.