Lyme meningitis is the direct result of invasion of the nervous system by Borrelia burgdorferi. Occurring within the first few months of infection, it initially presents as a chronic basilar meningitis. Much about the pathogenesis of Lyme meningitis has been learned from animal models, the best being the adult Rhesus macaque. Injection of these animals with a highly infective strain of B. burgdorferi has led to a very predictable course of events: erythema migrans within the first few weeks after injection, development of anti-B. burgdorferi antibody, detection of spirochetemia in weeks 3 and 4, and central nervous system (CNS) invasion within 1 month with cerebrospinal fluid (CSF) pleocytosis. In humans, facial palsy is the earliest clinical indicator. Headache and meningismus are symptoms of inflammation of the subarachnoid space. Severe fatigue and arthralgia are common extra-CNS symptoms. Culture is not generally useful for detecting or confirming Lyme meningitis. False-positive serologic tests may occur in patients with other infections, inflammatory processes, or malignancies. Immunoblotting will differentiate true-from false-positive antibody reactivity. Lack of a consistently positive serum antibody titer should make the diagnosis of Lyme meningitis suspect. Positive CSF antibody is almost universal in patients with Lyme meningitis. Polymerase chain reaction is a direct test that is highly specific and sensitive. The antibiotic treatment of choice is intravenous (i.v.) cephalosporins or penicillin for 2-3 weeks. If the clinical picture is anything less than absolutely classic, a lumbar puncture and Western blot of serum should be obtained in a seropositive patient before initiating intravenous antibiotic therapy. There is no role at this time for long-term (> 1 month) intravenous antibiotics. Nonsteroidal antiinflammatory agents can also be of benefit.