The relationship between a maternal dose of methadone and the incidence and severity of neonatal signs of withdrawal, placental transfer of drug, and the relationship between maternal and neonatal plasma levels of methadone were studied in 30 mothers and their infants. Plasma levels of methadone were analyzed using a gas chromatographic method. Our studies demonstrate that the relationship between maternal dose of methadone and the incidence of neonatal withrawal symptoms was closely related to the last maternal dose of methadone. The ratio of neonatal to maternal plasma concentrations of methadone was 2.2:1. Neonatal withdrawal symptoms appear to be related to individual variation in maternal metabolism of the drug, placental transfer of methadone, and most importantly, to the individual variations in the rate of excretion of methadone as reflected in the neonatal plasma t 1/2. At plasma levels of methadone greater than or equal to 0.06 mug/ml, the symptomatic patients appeared to be protected from withdrawal. When the plasma concentration fell below this level, withdrawal symptoms began within 24 hours.