Tick-borne infection caused by spirochete Borrelia burgdorferi. Classic target rash (primary erythema chronicum migrans) at site of tick bite occurs in < 50% of patients; sometimes followed by a secondary annular nonpruritic, nonpainful rash several weeks to months later at distant site, heralding systemic spread of spirochete. Physician confirmation of either type of rash mandates immediate treatment without delay. Signs and symptoms are multiple, with initial presentation possible in disseminated form. Disease may mimic multiple sclerosis (with pattern of demyelinated plaques in CNS indistinguishable from multiple sclerosis), juvenile rheumatoid arthritis, and ParkinsonÕs disease. Antibody tests (including Western blot) are notoriously unreliable and should never be used to rule out Lyme disease. PCR, urine, antigen, and culture tests are being used with increasing frequency but controversy remains regarding specificity and sensitivity. Diagnosis of Lyme disease mandates evaluation for ehrlichiosis and babesiosis coinfections. Controversy also exists regarding treatment protocols. Growing minority of Lyme experts favor prolonged, multiantibiotic regimens (doxy-cycline, cefuroxtime, azithromycin, ceftriaxone, metronidazole) for up to 18 months or until symptoms abate and ascribe existence of post-Lyme syndrome to inadequate treatment, Use of antibiotics usu. causes worsening of symptoms and excessive fatigue (Jarisch-Herxheimer reaction). Some clinicians treating this disease consider the lingering symptoms of Òchronic LymeÓ to be mediated by a Borrelia neuroloxin. They have reported success in blocking a-TNF release using an initial 10-day course of Actos, followed by several weeks to months of daily oral Questran (cholestyramine).