Ceftriaxone pharmacokinetics were determined in 40 newborn infants who were 1 to 45 days of age. Mean peak plasma concentrations of 136 to 173 micrograms/ml were observed at the completion of a 15-min intravenous infusion of 50 mg of ceftriaxone per kg. Mean half-life values were 5.2 to 8.4 h, and mean plasma clearances were 0.7 to 1.8 ml/min. Rectal swab cultures from 14 of 16 infants had either reduced numbers of aerobic and anaerobic bacteria or no growth during therapy. A once-daily dosage schedule is suggested for ceftriaxone therapy in newborn infants.