DESCRIPTION (provided by investigator): Because of absolute recommendation for annual vaccination for the most vulnerable populations (the elderly), only observational studies of vaccine effectiveness can be carried out among them for ethical reasons. Results from observational studies may be inaccurate due to unrecognized selection biases. Study design strategies to identify and adjust for these biases are necessary. The proposed observational study includes such strategies including laboratory- confirmation of medically attended influenza-like illnesses (ILI) as influenza, planned effectiveness estimates within and outside of surveillance defined periods of influenza circulation and new strategies to adjust for missing information that results in misclassification of outcome measures. Our primary objective is to assess annual effectiveness of licensed influenza vaccines in preventing laboratory-confirmed medically-attended influenza, including influenza-related complications. This assessment requires (1) identification of patient cohorts that are followed for outpatient health care contacts for acute respiratory illness (ICD-9-CM 460- 466) or pneumonia and influenza (ICD-9-CM 480-487), and hospitalization for pneumonia and influenza (ICD-9-CM codes 480-487); (2) collection of specimens from ill patients and laboratory processing of specimens using viral culture and real time PCR methods to confirm respiratory illnesses as influenza; (3) determination and validation of influenza vaccination status of cohort members; and (4) implementing a mechanism such that preliminary data for interim effectiveness estimates are available during the influenza season, with complete data available for summary analyses and publication by September following annual influenza seasons. Our secondary objective (5) is to recruit, vaccinate and collect paired pre- and post-vaccination blood specimens from 300-450 participants, 65 years and older, for assessment of the serologic (up to 450 participants) and cell-mediated (up to 150 participants) immune responses to influenza vaccination. All participants will receive a single dose of a licensed inactivated vaccine (timed appropriately for seasonal protection); paired blood specimens will be collected at pre- and 30-day post-vaccination visits, required immediate specimen processing performed and specimens stored in appropriate repositories until shipped to reference labs for testing.