Beta 2-microglobulin (beta 2m) determination in CSF of 72 neonates who underwent a spinal tap as part of a sepsis or meningo-encephalitis workup was performed to evaluate the usefulness of this test in the diagnosis of CNS infections. Beta 2m was measured by enzyme immunoassay. Sixty neonates had sterile culture and normal neurological status at discharge. Twelve infants had CNS infections: 8 bacterial meningitis, 3 TORCH infections (T = toxoplasmosis, O = others, R = rubella, C = cytomegalovirus and H = herpes simplex) and 1 viral meningitis. Neonates with CNS infection exhibited significantly higher CSF beta 2m levels compared to neonates with sterile culture (6.24 +/- 2.66 vs 1.74 +/- 0.5 mg/l; P < 0.0001). CSF beta 2m levels did not correlate with the white cell count, total protein concentration or glucose level in CSF. When serum and CSF levels were measured simultaneously, the CSF beta 2m level was significantly higher than the corresponding serum level in patients with CNS infection (6.98 +/- 2.5 vs 3.2 +/- 0.25 mg/l; P < 0.01). Sensitivity, specificity, and predictive values were estimated for different cut-off points. The best operational diagnostic cut-off value was 2.25 mg/l. Receiver operating characteristic curve analysis showed an appropriate trade-off between specificity and sensitivity and indicated that CSF beta 2m was accurate in distinguishing between neonates with and without CNS infection. Conclusion. CSF beta 2m may be a useful ancillary tool in neonates when CNS infection is suspected.