Although lead encephalopathy has virtually disappeared from the United States, thousands of children still have sufficient lead exposure to produce cognitive impairment. It is not known whether treating children with blood lead levels < 45 microg/dL (2.2 microM) is beneficial and can be done with acceptable safety. We conducted a 780-child, placebo-controlled, randomized trial of up to three courses of succimer in children with blood lead levels of 20-44 microg/dL (1.0-2.1 microM). Children were aged 12-33 mo, 77% were African-American, 7% were Hispanic, and they lived in deteriorating inner city housing. Placebo-treated children had a gradual decrease in blood lead level. Succimer-treated children had an abrupt drop in blood lead level, followed by rebound. The mean blood lead level of the succimer-treated children during the 6 mo after initiation of treatment was 4.5 microg/dL (95% confidence intervals, 3.7 to 5.3 microg/dL; 0.22 microM, 0.18 to 0.26 microM) lower than that of placebo-treated children. There were more scalp rashes in succimer-treated children (3.5% versus 1.3%) and an unanticipated excess of trauma. Succimer lowers blood lead level with few side effects. The unanticipated excess of trauma requires confirmation.