It is largely accepted that aminoglycosides play an important role in drug-induced nephrotoxicity in newborns, expecially in prematures. Serum creatinine and blood urea nitrogen (BUN) elevations are relatively late manifestations of nephrotoxicity, because the most common effect of aminoglycosides in the direct toxicity to renal tubular cells. Therefore, some urinary enzymes and some plasma proteins with relative low molecular mass have been recommended as usefull urinary markers for the detection of early pathological changes in the proximal tubule. α1-m levels and NAG activity as well as urinary creatinine were measured in urine samples of 28 preterm neonates (18 males and 10 females) divided into two groups group A consisted of 17 preterm infants traeted with ampicillin plus amikacin for suspected bacterial infection. Mean G.A. was 37.7±2.3 weeks, mean birthweigth 2072±592 g, a 1-min Apgar score of 6.7±1.7 and a 5-min Apgar score of 8.3±1.1. The control group B) it comprised 11 preterm newborns with mean gestational age of 32.5±1.7 weeks, mean birthweigh of 2017±606 g, 1-min Apgar score of 7.6±0.9 and 5-min Apgar score of 8.6±1.3. Twelve hours urine samples were collected over the first weeks of life in all the infants and immediately assayed. Urinaryα1-m concentration was measured by immunonephelometry (Behring Institute. Scoppito Italy); NAG activity was determined spectrophotometrically at 405 nm (FAR Diagnostic Division, Verona Italy). Creatinine was measured by the Ektachem enzymatic assay. All results were expressed as a ratio to urinary creatinine excretion. RESULTS: In the control group, urinary values ofα1-m and NAG ranged respectively from 12.3 to 20.2 g/mol creatinine and from 1.99 to 4.06 U/mmol, and were estable over the first week of life. In group A patiens, we noticed a progressive increase of urinary α1-m 48th hour after the beginning of the antibiotic treatment up to the 120th hour. NAG levels significantly increase 24 hours after the beginning of the antibiotic therapy up to 120th hours. The Kruskal-Wallis test was performed to compare results obtained in the two groups: we found a statistically significant difference (p-0,0005) between α1-m values in control group and those in group A, after the 60th hour from the beginning of therapy. Similarly, we found a statistically significant difference (p-0.0001) between NAG values in control group and those in group A after the 36th hour. These preliminary results suggest that urinary α1-m and NAG could be proposed as a simple, non-invasive method for the assessment of antibiotic-induced renal tubular dysfunction and injury.