The purpose of this study was to characterize the clinical features of laboratory-confirmed influenza in 20 children and young adults with cancer who were receiving immunosuppressive therapy. Viruses isolated from pharyngeal and nasopharyngeal cultures were identified as the A/Hong Kong/1/68 strain or one of its variants, either A/England/42/72, A/Port Chalmers/1/73, or A/Victoria/3/75. Although the signs and symptoms of influenza in our patients were not unusual, the clinical course lasted twice as long as in the general population. Complications developed in only 3 patients and were related to secondary bacterial infections rather than influenza. An important sequelae of influenza was the interruption of cancer therapy in 16 patients for periods of 4 days to 3 1/2 weeks. The severity of influenza did not appear related to type or activity of malignancy or to duration or specific form of cancer therapy. Guidelines for the prevention and management of influenza in children with cancer are recommended.