In 19 premature newborns (mean birth weight 1600 g, range 800-2430 g), receiving a daily dose of 100-150 mg piperacillin/kg body weight in four divided doses, serum concentration of the drug at the end of its interval of administration was a mean of 32.6 +/- 25.0 mg/l. In six mature newborns it was lower at 12.5 +/- 9.0 mg/l. The mean serum drug level on days 1, 5 and 10 in ten premature newborns at the end of the respective interval of administration was reduced to about 69% of the initial level. Elimination of piperacillin (half-life and clearance) was determined in the middle of their first week of treatment in 11 prematures. Compared with values in adults, mean half-life was increased fourfold. In individual cases it was increased tenfold. Compared with a control group of mature newborns, clearance was markedly reduced. Because of the danger of underdosage as a result of increasing maturation of elimination during the period of treatment, piperacillin should be given in slightly higher doses, 200-300 mg/kg in premature and mature newborns. However, the clearly prolonged half-life makes it possible to divide daily dosage into two doses.