Small intestinal absorptive function can be disturbed in iron deficiency. We examined the permeability behavior of the small intestinal mucosa toward lactulose and rhamnose in 26 otherwise healthy children with iron deficiency. Their (mean +/- SD) age was 21 +/- 8.6 months; hemoglobin 7.9 +/- 0.9 g/dl, mean corpuscular volume (MCV) 60.1 +/- 3.4 fl, serum iron 2.72 +/- 0.66 mumol/L, serum ferritin 7.3 +/- 1.6 micrograms/L. After an isotonic oral load of both sugars, their 5-h urinary excretion was measured by gas-liquid chromatography/mass spectrometry. The ratio of the percentage of urinary recovery of the sugars [lactulose/rhamnose (%)] was determined as the permeability index. The tests were repeated in the same subjects after 3 months of iron supplementation, and achievement of an iron sufficient state. In the iron-deficient state, the permeability index was significantly higher than the standard normal value (0.15 +/- 0.05 versus less than 0.07; p less than 0.01), but was not different from normal when the children had attained a normal iron status. The major factor for the alteration of the permeability index in the children with iron deficiency was a significantly lower urinary recovery of rhamnose (which passes the small intestinal epithelium by a transcellular route); the recovery of lactulose (which passes through a paracellular route) was not affected by iron deficiency. Our study indicates that iron deficiency in infants and young children can alter permeability characteristics of the small intestinal mucosa. Iron status should therefore be considered when interpreting permeability tests in the young.