Influenza is one of the most important respiratory diseases of mankind, yet scant data exist concerning the frequency and clinical course of influenza in severely immunocompromised adults. From October 1993 to September 1994, we cultured the respiratory secretions of all adults with leukemia who were hospitalized with an acute respiratory illness at The University of Texas M.D. Anderson Cancer Center in Houston. During a 9-week period from 29 November 1993 to 29 January 1994, influenza virus type A (H3N2) was isolated from 15 (33%) of these 45 hospitalized adults. Twelve (80%) of the cases of influenza were associated with pneumonia, and four patients (33%) with pneumonia died. Patients who died tended to have received chemotherapy more recently and to be more myelosuppressed. Autopsy examination in two cases revealed histopathologic changes consistent with viral pneumonia. During community outbreaks, influenza is a frequent cause of serious respiratory disease in hospitalized adults with leukemia. Effective prophylactic and therapeutic regimens need to be defined for immunocompromised patients.