The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 +/- 0.13 liter/kg (mean +/- standard deviation) and 1.1 +/- 0.6 h, respectively. The total body clearance of piperacillin was 0.19 +/- 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 +/- 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 +/- 1.9 microg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 +/- 236 mg (26.3% +/- 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.