Drug-abusing women have higher rates of pregnancy complications and an increased incidence of infants with lower birth weights and higher rates of congenital malformations and mortality than are seen within the general population. In addition, there is an increased prevalence for longer hospitalization due to neonatal abstinence syndrome. The risk of adverse events in drug-exposed infants can be directly influenced by dose, class of abused substance and time of intrauterine exposure. In addition, poly-drug use may also have an effect on the developmental outcome of the fetus. To better understand the role illicit and licit substances have on the developing fetus, it is necessary that we develop improved methods of detection and gain a better understanding of the transport process involved in the transfer of drug across the placental membrane. Limited data are available correlating the relationships between maternaldrug concentration in plasma, urine, saliva, sweat and hair to amniotic fluid, cord blood, fetal urine, meconium and fetal hair. We have designed several studies to investigate maternal and fetal drug disposition in a variety of biological fluid and tissues. Each maternal specimen provides a history of drug exposure at different stages of gestation. Fetal specimens offer unique information about prenatal drug exposure. Meconium begins to be formed in the 13th week of gestation and hair in the last trimester. Each matrix offers the opportunity to determine if drug concentrations in different matrices relate to maternal and neonatal outcome measures. In addition, due to the low concentrations of drugs in fetal matrices, it is necessary to develop sensitive and selective methods for detecting these compounds. Analytical methods are being improved to offer more sensitive and reliable methods of detecting the parent drug and metabolites of opiates, including buprenorphine and methadone, cocaine, methamphetamine, cannabinoids and nicotine in a variety of maternal and infant specimens. One of the analytical challenges in measurement of drugs following in utero exposure is that drug and metabolite profiles in neonatal specimens may be quite different than those found in adult biological fluids. This may be especially true for premature infants.