Twelve women with iron-deficiency anemia due to chronic loss of blood, but free from any other pathology that might alter the immune response, were studied. The patients were tested for cell immunity both in vitro, by B and T lymphocyte quantitation and by blastic transformation of the lymphocytes with phytohemagglutinin (PHA), and in vivo, by dinitrochlorobenzene (DNCB), tuberculin, trychophytine and varidase skin tests. The same tests were repeated after iron therapy and also applied to a group of 12 normal control subjects. The percent of T lymphocytes increased significantly from 55.1 to 66.0% after treatment, while the absolute values did not change. There was a significant decrease in both the number and percent of "null" lymphocytes after treatment. The percent and absolute number of B lymphocytes did not change after treatment. Blastic transformation indices were within the normal range both before and after treatment. Seven women who were DNBC-negative before treatment became DNBC-positive after iron therapy. Of the 5 patients who were tuberculin-negative before treatment, 2 became positive after iron therapy. Reactivity to trychophytine was observed in 3 patients before treatment as compared to 5 afterwards. Reactivity to varidase increased from 4 to 6 patients upon iron therapy. On the basis of changes in immunological reactivity observed after iron replenishment, we conclude that iron deficiency is an important factor in the genesis of the immunological alterations occurring in iron-deficiency anemia.