Most studies focusing on respiratory infections in immunocompromised children have been addressed to bacterial etiology. However, respiratory virus infections in this population can also lead to severe disease. The objective of this study is to evaluate the clinical significance of respiratory virus infections in children with cancer or human immunodeficiency virus (HIV) infection. Retrospective study conducted in a teaching hospital in Madrid. Medical records from children <or=14 years diagnosed with cancer or with HIV infection were reviewed. We analyzed demographic characteristics, clinical syndromes associated with the infection, need for hospitalization, treatment prescribed, and outcome. Fifty-three respiratory viral infections were identified: 26 (20%) in 129 HIV-infected children and 27 (12%) in 218 children with cancer. Twenty (38%) of the respiratory infections were nosocomial. Causal viruses were: respiratory syncytial virus, 43%; influenza A, 26%; adenovirus, 13%; parainfluenza virus, 13%; and influenza B, 4%. Thirty-three children were hospitalized: 14 (54%) with HIV infection and 19 (70%) receiving anticancer chemotherapy. Pneumonia occurred in 11 (34%) of the 33 hospitalized children. Four (21%) of the 19 hospitalized children with cancer, but none of the HIV-infected children, were admitted to the Pediatric Intensive Care Unit (P=0.096). Two children with cancer died. Common respiratory virus infections in children with cancer or HIV infection have a relevant morbidity. The fact that 40% of these infections are hospital-acquired emphasizes the need for isolation and preventive measures.