Forty preterm infants with maternal isoxsuprine exposure less than 24 hours delivery and 40 matched control infants were studied prospectively to determine the acute neonatal effects of maternal ISX exposure. The cord ISX concentration correlated inversely with the drug-free interval before delivery (P < 0.001). Cord ISX concentrations > 10 mg/ml were seen only with intravenous maternal therapy and a drug-discontinuance to delivery interval of two hours or less. The plasma half-life of ISX in neonates ranged from 1.7 to 8 hours; gestationally younger infants required a longer time for drug clearance. Ileus was 13 times more common in the ISX group and was not directly related to the cord ISX concentration. The incidence of hypotension and hypocalcemia rose directly with the cord ISX concentration, reaching 89% and 100%, respectively, when the cord ISX level exceeded 10 ng/ml. The incidence of respiratory distress syndrome was low in the ISX infants with low cord drug values, but increased to that of the control group when the cord ISX concentration reached > 10 ng/ml.