Sixty-five cerebrospinal fluid (CSF) samples from 54 infants and children with bacterial meningitis were analyzed for the presence of interferon (IFN)-alpha with a biologic assay. Of the 65 samples, 3 were positive (2-4 IU/mL) and only 1 of 56 collected early was at 4 IU/mL. These results suggest that some subtypes of IFN-alpha already reported as present in viral infections of the central nervous system are not detected in bacterial meningitis by our IFN assay. This difference may be helpful in differentiating bacterial from viral infections and also in evaluating the quality of the virologic investigation; moreover, the rarity of IFN-gamma in CSF in bacterial meningitis needs further investigation to understand its role in the pathogenesis of the disease.