Transmission electron microscopy was used to study urine sediment and renal tissue from Fischer rats treated with gentamicin or tobramycin 40 mg/kg/day or sterile water (control) subcutaneously for 5 or 10 days. Renal function was assessed by serum urea nitrogen and 24-hour creatinine clearance. Urine sediment was examined for myeloid bodies and renal tubule cells. After 5 days, the renal function was not different, but myeloid bodies, renal tubule cells, and abnormal renal morphology were found only in tobramycin-treated animals. After 10 days, serum urea nitrogen was higher (p < 0.05) and creatinine clearance lower (p < 0.01) in treated than control animals. Myeloid bodies and renal tubule cells were found uniformly in treated animals. Transmission electron microscopy kidneys revealed abnormalities in treated animals, but focal tubular necrosis was found only in gentamicin-treated animals. This study using urinary sediment transmission electron microscopy as a sensitive technique reveals that tobramycin produces earlier but less severe aminoglycoside nephrotoxicity than gentamicin. Renal pathological changes may occur despite the absence of major decreases in renal function.