Influenze infection is a significant cause of morbidity and mortality in immunocompromised hosts, but its importance in adult cancer patients is largely undescribed. We therefore conducted a prospective study of the incidence and clinical features of influenza infection in patients with acute or chronic leukemia. The cohort, which consisted of all adult leukemia patients undergoing remission-induction chemotherapy during the 1991–1992 influenza epidemic, was followed prospectively for development of signs and symptoms of acute infection of the upper or lower respiratory tract. Of these 294 patients, 111 received chemotherapy as inpatients and 183 as outpatients. Throat swabs and nasal washes for viral culture were obtained from all symptomatic patients, who were then followed until all signs and symptoms resolved. Symptoms of respiratory tract infection developed in 37 leukemia patients (13%). Among these, influenza (A/Beijing/H3N2) caused 3 (21%) of the 14 infections that developed during hospitalization but only 1 (4%) of the 23 that developed in the community (P=0.14). Influenza patients presented with fever, rhinorrhea, nasal congestion, headache, and myalgia; those with other infections presented with signs and symptoms of lower respiratory tract infection (productive cough, rales, or rhonchi). Development of pneumonia was common in influenza patients, 1 of whom died from a secondary fungal and gram-negative pneumonia. Influenza A virus infections accounted for a substantial protion of acute respiratory infections among adult leukemia patients during a community epidemic. Most infections appeared to be nosocomial and the most likely sources were visitors or hospital personnel. Immunization of house-hold contacts and hospital staff may reduce the risk of influenza infection and its pulmonary complications in leukemia patients.