This Supplement includes the proceedings of a symposium held on January 30, 2007, to address issues relating to the seasonality of respiratory syncytial virus (RSV) disease. RSV infects more than 90% of all children within their first 2 years of life resulting in >125,000 hospitalizations annually and representing the single most common cause of hospitalization among infants in the United States. Despite the frequency of RSV infection, mortality among hospitalized patients appears to be <500 deaths annually, due largely to the increasing sophistication of supportive respiratory care provided in pediatric intensive care units. Long-term complications associated with severe RSV disease early in life include recurrent wheezing, reactive airway disease, and abnormalities in pulmonary function testing. Whether prevention of severe RSV disease or actual RSV infection early in life will reduce such long-term complications is unknown. Annual RSV outbreaks in countries with temperate climates primarily continue between late fall through early spring. Data from virology laboratories, compiled by the Center for Disease Control and Prevention have demonstrated that Southern regions of the United States experience the earliest onset and the longest season relative to other areas of the country. Midwestern states typically experience the latest onset as well as the shortest RSV season. The onset and duration of the RSV season in the West and Northeast regions typically fall between that noted in the South and the Midwest. Bronchiolitis outbreaks are correlated closely with RSV detection and prospective studies have found that most hospitalizations for bronchiolitis are caused by RSV. However, within this overall national paradigm of RSV circulation, there may be considerable variation in season onset and offset from year to year and from one location to another. Approximately 3% of all infants in the first 12 months of life will be hospitalized because of RSV infection and most of these infants will be previously healthy, term infants. Development of a vaccine offers the best hope for ultimate control of this disease, but serious scientific and societal obstacles must be overcome before this becomes a reality. In the absence of a useful antiviral agent for treatment or chemoprophylaxis, passive immunoprophylaxis remains the most important means of lowering hospitalization rates and reducing the burden of RSV disease in infants. However, immunoprophylaxis is costly and the most efficient use of resources necessitates its judicious use. Increasing the cost-effectiveness of immunoprophylaxis can be accomplished by restricting its use to infants with the highest risk for severe RSV disease and by concentrating its use to times of most active RSV circulation. The intention of this supplement is to review and refine RSV epidemiology in the United States, to describe 3 areas of the country where RSV circulation differs from national trends, and to address variation in RSV epidemiology that may have clinical impact. The first article by Welliver provides a provocative treatise on meteorological conditions which may influence patterns of RSV circulation. Then, Henrickson and Hall describe the advantages and disadvantages of standard diagnostic techniques and contrast them with newer molecular methods for diagnosis of RSV infection. The article by Panozzo et al, updates results from the National Respiratory and Enteric Virus Surveillance System tracking seasonal and geographic RSV trends within the United States. Singleton et al, describe their observations and thoughts on seasonal variation of RSV hospitalizations in the Yukon-Kuskokwim Delta region of Alaska. Next, Fergie and Purcell describe their experience with RSV hospitalizations in Corpus Christi and San Antonio, Texas. Light then presents observations on RSV hospitalizations from 3 hospitals in Miami and contrasts that experience with the data from Florida as a whole. The supplement concludes with thoughts on how differing definitions of RSV seasonality and how seasonal and geographic variation might be incorporated into decisions regarding immunoprophylaxis so as to better reflect patterns of RSV circulation.