The occurrence of infection with respiratory syncytial (RS) virus and Mycoplasma pneumoniae was determined over a 6-year period among residents of Tecumseh, Michigan by isolation and serology. RS virus infection was detected for a variable time each year during the months extending from November to May. There was little viral activity in intervals between these periods of prevalence, which occurred on an alternating short-long cycle. Higher infection rates were detected in periods preceding the long interval than were detected in periods preceding the short interval. Viruses isolated from serial annual outbreaks did not show any sequential changes in antigens, although some variation in antigenic structure was apparent. Infections were common in school-age children, indicating the role of this population in transmission. Young girls were infected as often as young boys, suggesting that observed differences in occurrence of illness must be related to differences in expression of infection. In contrast to RS virus, M. pneumoniae did not appear and disappear annually, but like it, the school-age group was most heavily involved in infection.