Serologic testing in early Lyme disease is not reliably positive and delays in reporting of results may hinder accurate diagnosis. Clinical recognition of Lyme meningitis (LM) and differentiation from other forms of aseptic meningitis is a problem which few published data address. We performed a chart review of children hospitalized 1990-1996 using ICD-9 codes for aseptic meningitis and Lyme disease. 24 Lyme patients were believed to have CNS involvement; of these, 12 had documented CSF pleocytosis and positive Lyme serology and/or erythema migrans. 40 patients had culture proven viral meningitis (VM) (all but 1 enterovirus); most of these children were < 3 months old and had lumbar punctures as part of a “sepsis work-up”. 10 VM patients were > 2.5 years old and had age distribution similar to LM patients. This last group was compared with the documented LM group with respect to demographic features, clinical presentation and CSF parameters. No statistically significant differences were noted for any demographic variables, although LM cases occured mainly in the early summer. Woods exposure was more common with LM, but history of tick bite was not. The presence of nonspecific symptoms (e.g. headache, neck pain, lethargy) was not different, but the duration was significantly longer in LM. Children with LM had significantly more frequent history of EM rash, lower presenting temperatures (mean 36.6° vs 38.3°), and more frequent cranial nerve palsies (facial and oculomotor). All but one of the LM patients exhibited either papilledema, EM rash or cranial nerve palsies, findings absent in the VM group. On CSF analysis, the LM patients had a significantly smaller number of WBCs (mean 80 vs 301/mm3) and a smaller percentage of neutrophils(6% vs 40%), while protein and glucose concentrations did not differ. CONCLUSION: In a Lyme endemic area, Lyme disease is a common cause of aseptic meningitis in older children. Attention to pertinent epidemiological and historical data, along with physical and CSF findings, allows timely differentiation of LM from VM.