Significant symptoms of neonatal drug abstinence first occurred at between 2 and 4 weeks of age in seven infants. Irritability and tremulousness were the major late symptoms, and seizures occurred in four of the seven infants. One infant in whom the syndrome was not recognized showed progression of symptoms and died at 3 weeks of age. Although patterns of maternal drug-taking varied, methadone hydrochloride was taken in all cases; in two women, urine test findings confirmed methadone to be the only drug of abuse. Fetal accumulation and delayed excretion of the drugs may account for delayed onset of symptoms. Physicians caring for such high-risk infants should recognize the potential seriousness of this problem.