Piperacillin was administered to normal, healthy volunteers by an intravenous infusion over 30 min at dosage regimens of 12 gm daily (4 gm every 8 hr) and 24 gm daily (6 gm every 6 hr) for 5 consecutive days. Mean peak serum level after 12 gm daily was 244 ± 24 (SE) βg/ml and after 24 gm daily, 353 ± 7 βg/ml. After infusion the serum level declined monoexponentially in most subjects. On the 12‐gm daily dosage mean values were 60 min for half‐life (t½), 16 1 for volume of distribution, 188 ml/minfor body clearance, and 139 ml/minfor renal clearance. The same values on day 4 were 47 min, 12 1, 181 ml/min, and 125 ml/min; the volume of distribution was lower than on day 1. On the 24‐gm daily dosage regimen, tlh was 60 min; volume of distribution, 16 1; body clearance, 183 ml/min; and renal clearance, 101 ml/min on day 1 compared to 68 min, 15 1, 148 ml/min, and 71 ml/min on day 4, the last 2 being significantly lower than on day 1. High renal clearance values were observed at low serum concentrations and vice versa, suggesting saturation of the tubular secretion process at high piperacillin concentrations in serum.