The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days. The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion. Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose. Positive correlations between gestational age and clearance and elimination rate were detected. A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens. Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.