Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection in infants. The immune response plays a leading role in the severity of the disease. We hypothesized that severe RSV disease is associated with an impaired immune response characterized by low circulating T lymphocytes and plasma cytokine concentrations. Methods: We evaluate the in vivo immune responses of previously healthy infants with their first proven RSV-acute lower respiratory infection that required hospitalization. According to the clinical severity, defined by using a strict scoring system, the in vivo immune response was compared through the analysis of plasma cytokine values and the phenotyping of peripheral blood lymphocyte and natural killer (NK) cells. Results: Absolute blood cell counts of CD4+, CD8+, and CD19+ lymphocytes and NK cells were lower in subjects with RSV than in control infants. Lowest cell counts were observed in more severe RSV-infected infants. Significant