Inclusion Criteria:

You may be eligible for this study if you:

• Are at least 18 years of age.
• Are seronegative for antibodies against B. burgdorferi antigens by Western Blot at enrollment.
• Have documented history of acute Lyme disease.
• Have had a rash (erythema migrans) that resembles a bullseye. This skin aberration usually occurs after a tick bite in late spring, summer, or early fall and is sometimes accompanied by fatigue, fever, headache, mild stiff neck, arthralgia or myalgia.
• Have had one or more clinical features typical of Lyme disease acquired in the United States (see technical summary)
• Have had one or more of the following symptoms and conditions that have persisted for at least 6 months (but less than 12 years) and are not attributable to another cause or condition: a) widespread musculoskeletal pain and fatigue that began coincident with or within 6 months following initial infection with B. burgdorferi. b) certain neurologic symptoms including memory impairment and nerve pain, beginning within 6 months following initial infection with B. burgdorferi.
• Have had a physician-documented history of prior antibiotic treatment with a currently recommended antibiotic regimen.

Exclusion Criteria:

You will not be eligible for this study if you:

• Have previously enrolled in this study.
• Are pregnant, lactating, or unable to use birth control measures during the treatment period of this study.
• Are taking chronic medication that could interfere with evaluation of symptoms.
• Are taking or have taken various medications that could interfere with the evaluation of symptoms (see technical summary).
• Are hypersensitive to ceftriaxone or doxycycline.
• Have active inflammatory synovitis.
• Have another disease that could account for symptoms of acute Lyme disease.
• Have another serious or active infection.
• Are unable to tolerate an IV.
• Have tested positive for Borrelia DNA in plasma or cerebrospinal fluid at the time of initial evaluation for study.
• Have tested seropositive by Western Blot (these patients may be offered enrollment in seropositive study).