We identified 10 infants (mean +/- SD birth weight, 1000 +/- 500 g; gestation, 29 +/- 3 weeks; postnatal age, 24 +/- 19 days) who had Staphylococcus epidermidis meningitis despite unremarkable cerebrospinal fluid (CSF) blood cell counts and glucose and protein levels. Staphylococcus epidermidis meningitis was diagnosed if all the following criteria were satisfied: (1) a CSF culture positive for S epidermidis within 48 hours, (2) a blood culture positive for S epidermidis with antibiotic sensitivities identical to those of the CSF isolate, and (3) clinical symptomatology. Lumbar puncture yielded white blood cell counts lower than 10 x 10(6)/L in 8 infants. Two subjects had CSF white blood cell counts of 11 x 10(6)/L and 14 x 10(6)/L. Cerebrospinal fluid glucose (2.8 +/- 0.9 mmol/L) and protein (1.15 +/- 0.32 g/L) concentrations were also unremarkable. Infants were treated with parenteral antibiotics for 19 +/- 5 days. There was no mortality or short-term morbidity. Staphylococcus epidermidis is a recognized cause of nosocomial meningitis in low-birth-weight infants and frequently occurs without CSF abnormalities.