After administration of a loading dose, temocillin was infused intravenously into 5 volunteers for 3 hours (250 and 750 mg/h). A urine flow of more than 500 ml/h was maintained. The mean plasma concentrations were 131.4 and 220.7 mg/L during the lower dose and higher dose infusions, respectively, and protein binding decreased from 83% to 74% with this increase in plasma concentration. The renal clearance of the total drug increased from 29.0 ml/min (low dose) to 50.5 ml/min (high dose) [p less than 0.001], but after correction for protein binding the renal clearance of the unbound drug only increased from 169.1 to 197.0 ml/min (not statistically significant). The extrarenal clearance of temocillin was negligible. Blocking of tubular excretion by probenecid caused a maximum decrease of the renal clearance of temocillin from 34.1 to 22.4 ml/min. This maximum effect of 12.3 ml/min subsided by 1.7 ml/min/h. The renal clearance of the free drug decreased to 134.6 ml/min, slightly less than the creatinine clearance (158.1 ml/min). It may be concluded that even at high plasma concentrations of temocillin there is no saturation of the tubular transport mechanism, and that tubular excretion plays a relatively minor role in the renal excretion of the drug.