Using newborn and adult rats we tested the correlation between aminoglycoside dose, resultant serum and renal cortical concentrations and nephrotoxicity evidenced by creatinine in serum and urine, N-acetylglucosaminidase and beta 2 microglobulins in urine and sphingomyelinase in renal cortical tissue. Our data reveal that aminoglycoside nephrotoxicity is clearly more evident in adult rats despite significantly lower drug serum concentrations and in the presence of substantially higher renal cortical concentrations. These data indicate that high aminoglycoside serum concentrations are not causing nephrotoxicity but rather reflect secondary body accumulation of the drug associated renal damage.