This is a multi-center, prospective, natural history study designed to characterize West Nile Virus (WNV) disease, including functional and neurologic outcomes, in study participants with laboratory documented WNV infection that have symptoms consistent with WNV neuroinvasive disease or WNV fever. The objectives of the study are to: identify and describe the mortality and morbidity, specifically neurologic and functional outcomes of patients with WNV; characterize the clinical course and diverse manifestations of WNV disease; and assess the kinetics of humoral immune responses to WNV infection, and to correlate these responses with clinical outcomes. The study will enroll a proposed sample size 120 study participants ages 18 and older. All study participants will undergo a series of laboratory, neurologic, and physical examinations and will be followed prospectively for one year to characterize the spectrum and sequelae of WNV disease. When patients meet inclusion criteria, informed consent will be obtained, and blood will be collected to perform polymerase chain reaction (PCR), immunoglobulin (Ig)M, and IgG testing for WNV infection. Urine PCR for WNV will also be obtained. Upon enrollment (Day 1), a medical and surgical history, review of systems, travel, vector and blood product history will be obtained, and the baseline neurologic and clinical status will be evaluated. A clinical assessment, including a physical examination, vital signs and laboratory assessment will be performed. Based on history a pre-illness neurologic functional score will be estimated, using the Barthel Index (BI) and the Modified Rankin Scale (MRS). Investigators will assess a Day 1 functional score, using the BI, the Modified Mini-Mental Status Examination (3MS), the Glasgow Outcome Score (GOS), and the Glasgow Coma Scale (GCS) if hospitalized and recorded answers to questions abstracted from the MRS on the day of entry into the study. At study visit Day 1 ± 3, cerebrospinal fluid (CSF) will be obtained and tested for cell count, differential, protein and glucose, IgM, IgG and PCR for WNV infection. If a study participant has a lumbar puncture conducted for standard of care at any time up to 72 hours prior and up to 72 hours after study enrollment, a repeat lumbar puncture will not be necessary if an adequate aliquot of CSF is available for shipment to the Collaborative Antiviral Study Group (CASG) Virology Laboratory and if the required cell count, differential, protein and glucose tests were performed. A brain Magnetic Resonance Imaging (MRI) scan will be done on study visit Day 1 ± 3. If the brain MRI scan on study visit Day 1 ± 3 suggests abnormalities, a repeat MRI scan will be conducted at study visit Day 30 ± 5. If changes (either improvement or worsening) in the WNV related lesions have occurred since the MRI conducted on study visit Day 1 ± 3, a third MRI will be conducted on study visit Day 90 ± 14. Subsequent MRIs will be conducted at study visits 180 ± 21 and 365 ± 30 only if the WNV related lesions continue to improve or worsen: any two MRIs where the WNV related lesions remain stable will obviate the need for further MRI scans. There will be study visits at Day 1, Day 14 ± 3, Day 30 ± 5, Day 90 ± 14, Day 180 ± 21, and Day 365 ± 30. At these visits a brief physical examination will be done, a functional score will be assigned, and blood will be obtained for serologic WNV studies. Neurological endpoints will include the GCS and 4 validated functional and cognitive scoring scales: The BI, MRS, GOS, and 3MS. MRI of spinal cord, electromyogram and nerve conduction studies will be included when available.