The combination of sulbactam and ampicillin was administered to 16 newborn infants, 15 preterm and one term, who required umbilical arterial or venous catheterization and prophylactic antibiotics. The aims were to determine an appropriate dosage regimen and to study the pharmacokinetics. Satisfactory plasma concentrations were achieved with administration of a bolus injection of 50 mg of each drug/kg every 12 hr (mean concentrations: sulbactam, 110 mg/liter; ampicillin, 87 mg/liter 3 hr after dosing; and sulbactam, 105 and 135 mg/liter; ampicillin, 320 and 310 mg/liter 30 min after dosing in two infants. Mean elimination half-lives were longer than those in adults (sulbactam, 7.9 hr; ampicillin, 9.4 hr), and urinary excretion over 12 hr varied considerably (range: sulbactam, 7%-91%; ampicillin, 5%-132%), rates reflecting the immature renal function in the newborn and the relative oliguria characteristic of preterm infants with idiopathic respiratory distress syndrome. There was little evidence of accumulation of either drug, and both were well tolerated. This combination and dosage should be suitable for a trial of therapy for infection in the newborn.