A negative correlation between leptin and appetite or food intake has been shown in healthy individuals. However, the role of leptin in clinical conditions characterized by anorexia has not been established. One of the well-known clinical features of iron-deficiency anemia is poor appetite. We examined the-changes in plasma leptin levels in relation to expected improvement in appetite with iron treatment in children with iron deficiency. In 24 infants and small children (mean age +/- standard deviation = 19.6 +/- 7.7 months) with iron deficiency, we studied plasma leptin levels before and after iron therapy. After 15.0 +/- 2.4 wk of iron treatment, serum ferritin levels improved significantly, with accompanying increases in their subjective appetite scores and food intakes. However, as their mean age and plasma leptin levels adjusted their body mass indexes were unchanged. Serum ferritin correlated significantly with appetite score (r = 0.680, P < 0.001) and food intake (r = 0.480, P < 0.01). Leptin correlated only with body mass index (P = 0.405, P < 0.01). Lack of association between plasma leptin levels and degree of appetite in iron-deficient children treated with iron suggests a leptin-independent mechanism for the observed increase in appetite. (C) Elsevier Science Inc. 2001.