We studied the disposition of two 100 mg/kg doses of cefoperazone given intravenously 12 hr apart in ten newborn infants. Peak levels were a mean 352 ± SD 75 and 371 ± 68 μg/ml immediately after the first and second dose, respectively, with corresponding troughs of 60 ± 10 and 76 ± 28 mcg/ml 12 hr later. Mean half-life was 6.5 ± 0.9 hr and decreased with increasing gestational age and birthweight. Steady-state volume of distribution averaged 410 ± 40 ml/kg and total clearance 0.78 ± 0.13 ml/min · kg and neither varied with gestational age nor birthweight. No untoward physical or laboratory effects were noted. Additional studies including postnatal age effects on kinetics, efficacy, and cerebrospinal fluid penetrance are necessary prior to widespread use of this potentially valuable antibiotics in newborn infants.