Background: Acute viral respiratory infections represent a globally important cause of morbidity and mortality in childhood. An individual's cellular response appears to play a critical role in recovery from infections, given that individuals with impaired cellular immunity, congenital or acquired, have more severe diseases and secrete the virus for longer periods. Objectives: The aim of this study was to immunohistochemically evaluate the expression of the cell surface antigens CD4, CD8, CD25, CD14 and CD74, in pneumonic infiltrates in the alveolar septa using paraffin-embedded lung samples from autopsies of immunocompetent children who died of lethal, non-pandemic, severe acute respiratory infections. Study design: From 794 cases of pediatric autopsies of patients with severe respiratory disease (between 1960 and 2004), 193 cases were selected for this study. To identify subpopulations of inflammatory cells in the alveolar septa, cell surface antigen expression was assessed by immunohistochemistry using the following primary antibodies: anti-CD4, anti-CD8, anti-CD14, anti-CD25 and anti-CD74. Results: The TCD8+ lymphocyte count was higher in the virus-positive group (p = 0.04) and was also much higher among cases that were positive for more than three viral types (p = 0.016). There were fewer CD14+ cells in cases of AdV (adenovirus) infection (p = 0.002), and there was a predominance of CD74+ cells in the histopathological pattern defined as interstitial pneumonitis (p = 0.037). Conclusions: The results of this study demonstrate that TCD8+ lymphocytes present in the alveolar septa participate to a greater extent in the response toward viral pneumonia, while CD 14+ cell numbers are often reduced in cases of AdV.