This application proposes to study the pathogenesis of a post Lyme disease syndrome (PLS) which is characterized by chronic musculoskeletal pain, fatigue-and disordered cognition, resembling fibromyalgia (FM). The paradigm of an infection-induced FM syndrome offers the major advantage of conducting prospective studies from disease onset and determining host, infectious or immunologic factors that lead to the development of the condition. This will be a prospective as well as a cross-sectional study. In the prospective arm, l00 patients with the constitutional features of early Lyme disease will have genetic analysis(HLA typing); psychological and neurocognitive testing; SPECT brain scanning; blood and spinal fluid cultures and PCR analysis for Borrelia burgdorferi, and measurement of anti-Borrelial antibodies, anti-Borrelial containing immune complexes and lL-6 and lL-6 complexes. Somatomedin, a growth hormone-related peptide found to be low in FM serum, will also be measured. These patients will be followed after treatment, clinically for the development of PLS and FM and will undergo repeat SPECT scanning, psychological and neurocognitive testing, and blood testing every 8-12 months for 2 more times. In this way, it can be determined if host genetic and psychological factors play a role in predisposition to PLS and FM. Also, the role of B. burgdorferi and the immunological response to it in the development of PLS can be assessed. It may also be possible to correlate changes in cerebral blood flow by SPECT scanning to neurocognitive abnormalities and relate these to infectious or immunological central nervous system injury. In the cross sectional analysis, 25 PLS patients will be compared to age, gender and education matched controls. The control groups are 25 recovered Lyme disease patients, 25 spontaneous FM patients and 25 normal spouse controls. PLS patients and controls will be evaluated using all the above clinical, psychological, neurocognitive, imaging and serological tests. This will relate the abnormal findings in PLS to those in FM and should provide us with insights into the pathogenesis of FM