Respiratory syncytial virus (RSV) isolates obtained from nine infected immunocompromised adult patients hospitalized during two consecutive winters (January through April 1987 and 1988) were collected and analyzed against a panel of monoclonal antibodies by an enzyme immunoassay. The history of the patients' illness, onset of symptoms, and date of initial isolation of virus was correlated with the hospital ward and time of hospitalization. Three patients died of respiratory failure related to RSV infection acquired nosocomially. A cluster of RSV disease in four patients hospitalized simultaneously during the 1987 season was demonstrated to be caused by four antigenically distinct viruses; despite an epidemiologic link among the patients, each had been infected from a different source. The RSV disease in the five immunocompromised adults in 1988 was caused by two distinct strains; three patients were infected with RSV subgroup A/4, and two were infected with RSV subgroup B/2. Combining the epidemiologic and strain characterization studies, none of four patients in 1987 were infected from each other, and two of five patients in 1988 may have been infected, directly or indirectly, from one of the other five. The strain characterization studies demonstrated the potential complexity of RSV nosocomial transmission and the need to consider a number of sources for transmission in developing effective prevention strategies. The three deaths underscore the importance of nosocomial RSV disease and the importance of effective prevention strategies.