Although this observational study cannot prove epidemiological causality, our analysis of seasonal oscillation in IPD and influenza A and B incidence in Ontario, Canada, is strongly suggestive of a causal relationship between influenza and IPD. The fact that we did not find a relationship between seasonal dynamics of influenza and IPD suggests that this relationship likely results from effects of influenza on risk of invasive disease in individuals with pneumococcal colonization. We found no epidemiological evidence to support the concept that influenza has a strong effect on IPD risk via changes in pneumococcal transmission dynamics that would be caused by enhanced susceptibility to pneumococcal colonization, increased infectiousness of pneumococcus-colonized individuals, or increased duration of carriage. All such changes would be expected to perturb the dynamics of pneumococcal seasonality in such a way that pneumococcal seasonal waves would ''track'' influenza waves. While we found significant and temporally directional relationships between influenza burden in the population and IPD risk, the seasonal ''waves'' of influenza and IPD were independent of one another, with substantial variability in influenza contrasted with the far more regular seasonal occurrence of IPD. The nonstereotyped nature of wintertime seasonality of viral respiratory pathogens has been noted previously [17] .