While hospitalization rates have declined overall, hospitalizations for acute lower respiratory tract infections have increased steadily since 1980. Development of new approaches for prevention of acute respiratory tract conditions requires studies of the etiologies of infections and quantification of the risk of hospitalization for vulnerable patients. To determine the frequency of specific virus infections associated with acute respiratory tract conditions leading to hospitalization of chronically ill patients. Analysis of viral etiology of patients hospitalized with acute respiratory tract conditions between July 1991 and June 1995. Four large clinics and related hospitals serving diverse populations representative of Harris County, Texas. A total of 1029 patients who were hospitalized for pneumonia, tracheobronchitis, bronchiolitis, croup, exacerbations of asthma or chronic obstructive pulmonary disease, and/or congestive heart failure. Virus infection, defined by culture, antigen detection, and significant rise in serum antibodies, by underlying condition; hospitalization rates by low- vs middle-income status. Ninety-three percent of patients older than 5 years had a chronic underlying condition; a chronic pulmonary condition was most common. Patients with chronic pulmonary disease from low-income populations were hospitalized at a rate of 398.6 per 10000, almost 8 times higher than the rate for patients from middle-income groups (52.2 per 10000; P<.001). Of the 403 patients (44.4% of adults and 32.3% of children) who submitted convalescent serum specimens for antibody testing, respiratory tract virus infections were detected in 181 (44.9%). Influenza, parainfluenza, and respiratory syncytial virus (RSV) infections accounted for 75% of all virus infections. Our study suggests that respiratory virus infections commonly trigger serious acute respiratory conditions that result in hospitalization of patients with chronic underlying conditions, highlighting the need for development of effective vaccines for these viruses, especially for parainfluenza and RSV.