To better understand patterns of medication use in neonatal intensive care, we examined data collected prospectively over a recent 9-year period in the newborn intensive care units of two large teaching hospitals. Among 2690 infants studied, 91% received at least one drug; 99% of infants weighing less than 1500 gm were exposed to drugs, compared with 90% of infants weighing more than 1500 gm. Among treated infants, the median number of drugs received was eight; the number of drugs administered was inversely related to birth weight and directly related to both length of hospital stay and the complexity of the infant's clinical condition. Within categories of length of hospital stay, the number of drugs received per day was greatest during the first week in the neonatal intensive care unit and fell to a relatively stable lower level during the second week. The most commonly used single drug was gentamicin (71% exposed), followed by sodium chloride (60%), potassium chloride (59%), heparin (58%), and packed erythrocytes (45%). Between 1978-1979 and 1985-1986 the prevalence of use increased substantially for some drugs (ampicillin, morphine, calcium salts, and acetates of sodium and potassium) and decreased for others (kanamycin, sodium bicarbonate, and blood products). These data document the dynamic nature of drug therapy in the neonatal intensive care unit and provide information that can guide cost-benefit assessments in this setting.