The purpose of this study was to evaluate the sensitivity and specificity of laboratory methods in the diagnosis of posterythropoietin-era, iron-deficient, chronic renal failure patients. The patient population comprised 25 anemic (hemoglobin < 11 g/dL) patients with creatinine greater than 3 mg/dL; 20 were dialysis patients, two were transplant patients, and three patients had renal failure from other causes. Criteria for study inclusion were as follows: bone marrow iron was the reference standard and was graded 0 to +4, ranging from absent to diffuse homogeneous iron staining; serum ferritin concentration and serum transferrin saturation were tested in terms of sensitivity and specificity. The reference standard indicated that iron deficiency existed in 40% of patients. Neither serum ferritin nor transferrin saturation were completely adequate diagnostic tools. Serum ferritin levels less than 200 ng/dL were 100% specific for the diagnosis but only 41% sensitive. Transferrin saturation of less than 20% was 88% sensitive, but only 63% specific. By excluding patients with hypoproteinemia (transferrin values of < 150 mg/dL), the sensitivity of the test increased to 100% and the specificity to 80%. We conclude that transferrin saturation is an adequate screening tool in anemic chronic renal failure patients, provided that hypoproteinemia is not present. By determining both the serum ferritin concentration and the transferrin saturation, a high sensitivity and specificity can be achieved, even in patients with hypoproteinemia. Furthermore, we believe that on this basis, iron therapy in patients with renal insufficiency can be improved.