This study estimates the burden of respiratory syncytial virus (RSV) infection in young children in the United States. It involved prospective surveillance of acute respiratory infections in three U.S. counties from 2000 to 2004. RSV was detected in 919 of 5067 children, with RSV associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most children had no coexisting illnesses, and only prematurity and young age were independent risk factors for hospitalization. RSV-associated outpatient visits were three times higher than emergency department visits. Outpatients had moderately severe RSV-associated illness, but only 3% of cases were diagnosed as RSV. RSV infection is associated with significant morbidity in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children may have limited effect on the total disease burden of RSV infection. The study highlights the need for effective vaccines and better understanding of RSV's impact on previously healthy children. The findings indicate that RSV infection is a major cause of hospitalizations and outpatient visits among young children, with a significant burden on healthcare resources. The study also shows that RSV infection is more prevalent in younger children and that the burden is not fully recognized by healthcare providers and public health officials. The results emphasize the importance of addressing RSV infection in previously healthy children, as it imposes a larger burden than previously recognized. The study provides a comprehensive view of the RSV burden among children under 5 years of age, highlighting the need for further research and public health interventions.This study estimates the burden of respiratory syncytial virus (RSV) infection in young children in the United States. It involved prospective surveillance of acute respiratory infections in three U.S. counties from 2000 to 2004. RSV was detected in 919 of 5067 children, with RSV associated with 20% of hospitalizations, 18% of emergency department visits, and 15% of office visits for acute respiratory infections from November through April. Average annual hospitalization rates were 17 per 1000 children under 6 months of age and 3 per 1000 children under 5 years of age. Most children had no coexisting illnesses, and only prematurity and young age were independent risk factors for hospitalization. RSV-associated outpatient visits were three times higher than emergency department visits. Outpatients had moderately severe RSV-associated illness, but only 3% of cases were diagnosed as RSV. RSV infection is associated with significant morbidity in both inpatient and outpatient settings. Most children with RSV infection were previously healthy, suggesting that control strategies targeting only high-risk children may have limited effect on the total disease burden of RSV infection. The study highlights the need for effective vaccines and better understanding of RSV's impact on previously healthy children. The findings indicate that RSV infection is a major cause of hospitalizations and outpatient visits among young children, with a significant burden on healthcare resources. The study also shows that RSV infection is more prevalent in younger children and that the burden is not fully recognized by healthcare providers and public health officials. The results emphasize the importance of addressing RSV infection in previously healthy children, as it imposes a larger burden than previously recognized. The study provides a comprehensive view of the RSV burden among children under 5 years of age, highlighting the need for further research and public health interventions.