The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmacotherapy for the treatment of withdrawal symptoms. Phenobarbital, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants born to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the neonatal abstinence scoring system. Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paragoric, phenobarbital (titration), phenobarbital (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were defined: paregoric (n = 21); phenobarbital (n = 17); more than one agent (n = 31); and no treatment (n = 16). Data for the phenobarbital loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in group III since diazepam as a single agent was not successful. Results of one way analysis of variance revealed no differences in developmental status between groups (p greater than 0.10, F = 0.25). Scores for all groups were well within the normal range of development.(ABSTRACT TRUNCATED AT 250 WORDS)