We studied the pharmacokinetics of piperacillin in 37 preadolescent children (mean age 52 months,range 1 month to 11 years) after 50 mg/kg IV doses. Pharmacokinetic parameters were determined after the initial dose in 18 instances and after subsequent doses in 32 instances. There were no significant differences between the initial doses and the subsequent doses in the plasma piperacillin concentrations at comparable times, the elimination rate constants, the elimination-phase plasma half-lives, the total body clearances, the apparent volumes of distribution, or the areas under the concentration curves. At the end of a 30-minute infusion of the drug, the plasma concentration was 166.2±42.2 mg/L (mean ± SD) and ranged from 91.6 to 268.3 mg/L. The mean half-life was 31.0±9.4 minutes. The half-life of piperacillin in children 1 to 6 months of age (47.2 minutes) was significantly longer than in older children (28.8 minutes) (P<0.05). Likewise, the total body clearance of the drug in the younger age group (71.7 ml/min/m2) was significantly lower than in the older children (130.8 ml/min/m2) (P<0.05). The mean renal clearance of the drug was only 63% frange 39% to 85%) of the total body clearance, suggesting a variable but substantial nonrenal route of elimination. The intravenous administration of 50 mg/kg piperacillin every four hours results in adequate plasma concentrations for the treatment of most infections caused by gram-negative and gram-positive organisms.