Recombinant human erythropoietin has been demonstrated to significantly increase autologous blood procurement. To determine the importance of dietary or prescribed iron absorption, we analyzed iron-restricted erythropoiesis in this setting. No differences were found when premenopausal placebo and erythropoietin treatment groups were compared for hematocrit changes, number of units donated, percentage of phlebotomies deferred, and total blood volume procured. Seven of 10 women who had not reached menopause donated more blood iron than the apparent amount of total mobilizable iron available, demonstrating that dietary or prescribed iron had to be absorbed to donate the amount of blood iron stored. Thus oral iron absorption can potentially be a limitation to erythropoiesis in the presence of erythropoiesis therapy in women who have not reached menopause. In contrast, none of 16 women who had reached menopause and only two of 21 men required oral absorption of dietary or prescribed iron for the amount of blood iron donated. We conclude that although oral iron supplementation may not be necessary in men and in women who have reached menopause, alternatives to oral ferrous salt supplementation could be tested to determine whether such alternatives would improve the response to erythropoiesis in premenopausal women.