Objective: To evaluate the efficacy of oral D-penicillamine therapy in children with high blood lead concentrations. Design: A prospective, uncontrolled study. Methods and Patients: Seven children (2-16 y old; mean 8.7) with elevated blood lead concentrations but no symptoms of lead poisoning were treated with oral D-penicillamine. Lead-contaminated homemade flour was found to be the source of poisoning. Mean ± SD blood lead concentrations pilot to therapy were 60.3 ± 12.9 μg/dL (range 47.8-83). Mean blood zinc protoporphyrin (ZPP) was 337.86 ± 58.55 μmol/mol hemoglobin (Hb) (range 247-394). Results: Ninety days of treatment with D-penicillamine lowered the mean blood lead concentration by 31.7% to a mean of 40.7 ± 8.6 μg/dL (range 30-53)and lowered mean ZPP blood concentrations by 40% to a mean of 201.14 ± 14 μmol/mol Hb (range 150-278). Three patients with blood lead concentrations > 45 μg/mL at the end of this therapy were subsequently treated with succimer, an alternative oral chelator; the blood lead concentrations were further reduced to < 45 μg/mL. Conclusions: D- Penicillamine therapy significantly reduced blood lead concentrations but did not achieve acceptable lead and ZPP concentrations for young children. Therefore, we conclude that 90 days of D-penicillamine treatment is of limited effectiveness in young children who have high blood lead concentrations and also show symptoms of lead poisoning.