Aminoglycosides are inactivated by extended-spectrum penicillins in vitro and in patients with end-stage renal failure. In this prospective controlled study, we determined the effect of piperacillin on tobramycin pharmacokinetics. In 10 clinically stable male patients with calculated creatinine clearances of greater than or equal to 60 ml/min, serial levels in serum of tobramycin alone and after single 4-g intravenous doses of piperacillin were determined. No statistically significant changes in the concentration of drug in serum, the half-life (t1/2), the elimination rate constant (Ke), the volume of distribution (Vd), or the area under the serum concentration-time curve (AUC0-oo) occurred when tobramycin was used concurrently with piperacillin. Therefore, this antibiotic combination will not result in a clinically significant interaction in patients with normal renal function.