The nephrotoxicity, as measured by urinary cell and enzyme excretion, of vancomycin was studied in rats. The lowest daily iv dose inducing significantly increased cell elimination was 25 mg/kg. Im administration caused less effects probably due to incomplete absorption from the im injection site, since im dosages of 100 mg/kg daily led to lower renal tissue concentrations than the same doses given iv. Nephrotoxicity of vancomycin increased when combined with tobramycin and was reduced when combined with D-glucaro-1.5-lactam, a beta-glucuronidase inhibitor. Vancomycin accumulated in renal tissue during repeated administration.