We examined the relation of invasive pneumococcal disease to season, atmospheric conditions, and the rate of respiratory virus isolation in a community-wide surveillance program in Houston. Among adults, the number of cases of pneumococcal bacteremia peaked in midwinter and declined strikingly in midsummer, indicating a high degree of inverse correlation with the ambient temperature. We detected significant correlations between the occurrence of pneumococcal disease and the isolation of respiratory syncytial virus (P < .001), influenza virus (P < .001), and all viruses except influenza virus (P < .001), as well as with air pollution, as measured by SO2 levels (P < .001). In contrast, the rate of invasive pneumococcal disease among infants and children was relatively more sustained from October through May, with a notable decrease in summer months; the incidence of pneumococcal disease was therefore less strongly correlated with cold weather and less closely associated with the isolation of respiratory syncitial virus or influenza virus. However, pneumococcal disease among infants and children was associated with isolation of these viruses after a 4-week lag period as well as with isolation of adenovirus and ragweed pollen counts. The finding, with regard to children, that correlations tended to be stronger for events that occurred 1 month previously than for those that occurred contemporaneously is consistent with the concept that viral or allergic events predispose to otitis media with effusion, which becomes suppurative and leads to pneumococcal bacteremia or meningitis. For adults, a more immediate predisposition to pneumococcal pneumonia and bacteremia because of viral infection or air pollution was suggested.