In order to evaluate serum amyloid A as an early diagnostic marker of late-onset sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40 healthy matched controls were assayed for serum amyloid A. In parallel, clinical and biochemical variables that are used to evaluate neonatal sepsis were compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels were elevated in the sepsis group (187.6 +/- 78.3 micrograms/ml), compared with infants who had no sepsis (10.2 +/- 8.3 micrograms/ml) and the control group (6.9 +/- 3.3 micrograms/ml), and were significantly higher in gram-negative compared to gram-positive sepsis (221.8 +/- 84.4 micrograms/ml vs. 48.5 +/- 22.2 micrograms/ml). Analysis of the data suggests serum amyloid A has the highest sensitivity (100%), specificity (93%) and positive predictive value (96%) for sepsis among the clinical and biochemical parameters that were tested. In conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis of late-onset sepsis in preterm infants.