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The effect of iron therapy on malarial infection was investigated in Papua New Guinea, where malaria is endemic. Prepubescent schoolchildren with hemoglobin levels of 8–12 g/dl were randomly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks. Iron status and malarial infection were assessed at baseline, after 6 and 16 weeks of therapy, and 8 weeks after therapy was discontinued. Iron status was significantly improved by the treatment. The treatment did not significantly affect parasite rate, parasite density, or levels of anti-malarial IgG. No changes in spleen size were observed in either group. Furthermore, there was no significant difference between the groups in reported episodes of suspected malaria during the therapy. These results suggest that, in malaria endemic areas, oral treatment for iron deficiency can be carried out in semi-immune or immune schoolchildren without adverse consequences.