The effectiveness of elemental, nontoxic carbonyl iron in replacing iron lost at blood donation was examined. In a randomized double-blind design, 99 women, aged 18 to 40, were given placebo or low-dose carbonyl iron (100 mg orally) at bedtime for 56 days after phlebotomy. Compliance was equivalent for the two regimens. Mild side effects were slightly greater with carbonyl iron. At Day 56, estimated net iron absorption from therapy or diet, or both, was sufficient to replace iron in 85 percent of those receiving carbonyl iron but in only 29 percent of those taking placebo (p less than 0.001). The rates of deferral from repeat donation were 8 percent in the carbonyl iron group and 36 percent in the placebo group (p less than 0.01), and the positive predictive value of routine screening in identifying participants without iron deficiency was 83 versus 13 percent (p less than 0.01). It can be concluded that short-term carbonyl iron supplementation in female blood donors can replace the iron lost at phlebotomy, protect the women against iron deficiency, and enhance their ability to give blood.