The first dose and steady state pharmacokinetics of vancomycin were studied in 16 seriously ill preterm infants (less than or equal to 34 wk gestational age) with documented Staphylococcus epidermidis infections. One infant was dropped from the study due to peripheral flushing occurring during administration of the first dose. Individual vancomycin doses ranged from 9.8 to 17.8 mg/kg and were infused intravenously over 15-37 min. Fifteen infants were studied after the first dose of vancomycin, whereas only 12 of these 15 were able to be studied under steady state conditions. Vancomycin half-life, steady-state volume of distribution, and body clearance averaged 6.0 h, 0.53 liter/kg, and 1.22 ml/min after the first dose and only slight differences were observed in these parameter estimates under steady state conditions. However, substantial accumulation of vancomycin in serum was observed with multiple dosing. Complete 8-h urine collections were possible in 12 of 15 premature infants after the first dose of vancomycin. Overall, 44.6% of the dose was recovered in the urine with a corresponding vancomycin renal ClR averaging 0.88 ml/min. Vancomycin body Cl correlated directly with renal ClR (r = 0.88, p less than 0.001) and body weight (r = 0.8, p less than 0.001). Vancomycin pharmacokinetic parameter estimates Vdss and Cl correlated directly with body weight, surface area, and postconceptional age. No significant relationships were observed between these parameter estimates and gestational age or postnatal age. Fourteen of 15 infants were treated successfully for their underlying infectious process. These data support the use of lower doses of vancomycin than previously recommended for the treatment of preterm infants.