Gentamicin sulfate was given to rabbits for four weeks in two dosage regimens, either 4 or 8 mg/kg subcutaneously twice a day. Two of the seven animals in each group regained nearly normal renal function after a transient rise in the level of serum creatinine, but the remainder developed severe renal failure leading to the death of all but one of these rabbits. None of the animals showed significant hyperglycemia, but glycosuria appeared in all and was significantly correlated with the extent of renal damage. These findings demonstrate gentamicin-induced derangement of proximal tubular function and thus amplify the previously demonstrated histologic changes due to the drug. When the drug was administered twice daily, there was marked nephrotoxicity in rabbits given dosages of gentamicin only slightly higher than those employed clinically.