OBJECTIVES: To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. DESIGN: Observational. SETTING: Thirty-three Boston-area LTCFs over a 3-year period. PARTICIPANTS: Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. MEASUREMENTS: Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. RESULTS: A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P=.007), pneumonia (P=.02), and any lower respiratory tract infection (P=.002) was significantly associated with having a viral diagnosis. CONCLUSION: A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations.