Multiple factors have been implicated in the hematologic response to erythropoietin (EPO). The authors studied 54 hemodialysis patients; 44 received 1.5 g of iron intravenously, 16 received oral iron for 12 weeks, and 24 were treated with EPO. Some patients received these treatments in sequence. The factors evaluated were serum albumin, protein catabolic rate, serologic evidence of hepatitis B or C, parathormone (PTH), and aluminum levels. Red cell production was expressed as milliliters of red blood cell increase per day per kilogram of body weight. For patients receiving EPO, hematologic response was normalized to 50 U/kg/dialysis. Of the patients on oral iron, 31% had a good response (hematocrit greater than or equal to 30%). Of the patients who received iron intravenously, 50% had a good response (hematocrit greater than or equal to 30%). All patients treated with EPO responded well, except for one patient who did not respond to doses of EPO up to 200 U/kg/dialysis. The response to intravenous iron dextran was more rapid than the response to oral iron or EPO. Nutritional factors (serum albumin and protein catabolic rate), serologic evidence of hepatitis, elevated PTH levels, or elevated aluminum levels did not significantly affect the response to iron supplementation or EPO treatment.