This substudy of a longitudinal prospective study was designed to assess neurodevelopmental and neurobehavioral performance in newborn infants who were maternally exposed to cocaine and other drugs of abuse or the other drugs without cocaine. Sample selection procedures were designed to permit statistical control for marijuana, alcohol, and tobacco. Cocaine was assessed with both self-report and radioimmunoassay of hair. One hundred ninety-one newborns with a mean age of 43 h were assessed for 35 to 40 min on tests of reflexes, activity level, head-turning preference, tremors, nonnutritive sucking, habituation, and state. The testers were blinded to the baby's drug exposure. Cocaine-exposed newborns were developmentally at risk on the tests administered compared to infants exposed to the other three drugs alone or in some combination. A dose-response effect was found: higher amounts of cocaine were associated with higher neurobehavioral risk scores.