Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive inattention and/or hyperactivity-impulsivity. It has been suggested that ADHD symptoms are associated with restless legs syndrome (RLS), which is a neurological condition that is defined by an irresistible urge to move the legs. Increasing evidence suggests iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD and with RLS. To further define the relationship between iron deficiency and RLS in children and adolescents with ADHD, we evaluated 87 ADHD subjects: 79 boys and 8 girls with age 9.3 +/- 2.5 years (6-16 years). Various psychopathologies and the severity of the ADHD symptoms and serum ferritin levels were assessed. Diagnosis of RLS was made according to the International RLS Group criteria. The patients were evaluated for the iron deficiency (ferritin < 12 ng/ml). RLS was found in 29 (33.3%) of the 87 ADHD subjects. Parent- and teacher-rated behavioral and emotional problems and the severity of ADHD symptoms were not significantly different between ADHD subjects with RLS and those without RLS (n = 58). The rate of iron deficiency was significantly higher in ADHD subjects with RLS (n = 6, 20.7%) when compared with ADHD subjects without RLS (n = 1, 1.7%, p = 0.005). Our results showed that depleted iron stores might increase the risk of having RLS in ADHD subjects. Iron deficiency, which is associated with both ADHD and RLS, seems to be an important modifying factor in the relationship between these two conditions.