A large-scale, prospective drug screening of newborns by meconium analysis was done to determine more accurately the prevalence and epidemiologic characteristics of drug use in a high-risk urban, obstetric population. Every other neonate delivered in a perinatal center from November 1988 to September 1989 was prospectively enrolled and their meconium was analyzed by radioimmunoassay for the metabolites of three commonly abused drugs--cocaine, morphine (opiates), and cannabinoid. In 3010 subjects studied, 44% were positive for cocaine, morphine, or cannabinoid; 31% were positive for cocaine, 21% for morphine, and 12% for cannabinoid. In contrast, only 335 (11%) mothers admitted to illicit drug use: 52% of their newborns had a positive urine drug screen and 88% had a positive meconium drug screen. Prevalence of drug use among the pregnant women varied per month. A profile of the pregnant addict in the population studied was noted (P less than .001): service patient, single, multigravid (greater than 3), and little or no prenatal care. The major problems associated with drug use during pregnancy were principally noted in the group that was exposed to cocaine and opiates and in the group where the mothers admitted to the use of illicit drugs. On the other hand, a large number of neonates who have been exposed to drugs in utero, particularly those whose mothers denied the use of drugs, appear normal at birth and may not be recognized. Improved detection of these newborns at risk can be achieved with a high index of suspicion and meconium drug analysis.