Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.