• The nephrotoxicity of the aminoglycoside amikacin sulfate was evaluated in an open, controlled study of newborns with presumed neonatal sepsis. One hundred twelve neonates were randomly allocated to receive either amikacin-ampicillin or mezlocillin, a semisynthetic penicillin. Neonates receiving amikacin, in contrast to those receiving mezlocillin, showed significant nephrotoxicity as evidenced by a delayed postnatal fall in mean serum creatinine level (82 to 80 μmol/L [0.93 to 0.90 mg/dL] vs 84 to 72 μmol/L [0.95 to 0.82 mg/dL]) and a delayed postnatal rise in mean creatinine clearance per kilogram of body weight (12% vs 38%). Furthermore, 40% of neonates receiving amikacin-ampicillin compared with 19% of neonates receiving mezlocillin had a decline in creatinine clearance (>25%). There was no relationship between amikacin nephrotoxicity and either peak or trough amikacin levels. In summary, in a controlled study of the use of amikacin and mazlocillin in neonates, the combination of amikacin and ampicillin proved more nephrotoxic to the newborn kidney.