The effect of iron deficiency on the jejunal mucosa was studied in postweaning rats that had received a 3-wk regimen of either iron-deficient or iron-sufficient diet (iron content 6 and 50 mg/kg diet) and in rats given the iron-sufficient diet for 1 wk after the initial 3-wk iron-deficient diet. Morphometric analysis showed little difference in villous height but a significant decrease in mitotic index of the crypt epithelial cells in the iron-deficient group. Direct immunoperoxidase studies showed that iron-deficient rats had substantially fewer sIgA- and IgM-containing cells than iron-sufficient rats. This abnormality was reversed after a 1-wk iron-sufficient diet. We conclude that iron deficiency may impair local immunity in the intestinal mucosa, sensitizing the surface epithelial cells to damage by noxious agents. Similar changes might lead to the syndrome of iron-deficiency anemia and hypoproteinemia in children.