The role of climate forcing in the population dynamics of infectious diseases has typically been revealed via retrospective analyses of incidence records aggregated across space and, in particular, over whole cities. Here, we focus on the transmission dynamics of rotavirus, the main diarrheal disease in infants and young children, within the megacity of Dhaka, Bangladesh. We identify two zones, the densely urbanized core and the more rural periphery, that respond differentially to flooding. Moreover, disease seasonality differs substantially between these regions, spanning variation comparable to the variation from tropical to temperate regions. By combining process-based models with an extensive disease surveillance record, we show that the response to climate forcing is mainly seasonal in the core, where a more endemic transmission resulting from an asymptomatic reservoir facilitates the response to the monsoons. The force of infection in this monsoon peak can be an order of magnitude larger than the force of infection in the more epidemic periphery, which exhibits little or no postmonsoon outbreak in a pattern typical of nearby rural areas. A typically smaller peak during the monsoon season nevertheless shows sensitivity to interannual variability in flooding. High human density in the core is one explanation for enhanced transmission during troughs and an associated seasonal monsoon response in this diarrheal disease, which unlike cholera, has not been widely viewed as climate-sensitive. Spatial demographic, socioeconomic, and environmental heterogeneity can create reservoirs of infection and enhance the sensitivity of disease systems to climate forcing, especially in the populated cities of the developing world.M any infectious diseases, especially those infectious diseases that are water-borne and vector-borne, have been shown to exhibit significant interannual variability in the size of seasonal outbreaks (e.g., 1-6). Identification of climate factors shaping interannual and seasonal variability is prerequisite to an understanding of the basic transmission biology of these environmentally driven diseases, and of their response to climate change. The impact of climate factors on the population dynamics of infectious diseases has typically been addressed at large spatial scales by aggregating surveillance data over whole countries, regions, and cities (e.g., 3, 4, 6-8). Global climate drivers, such as the El Niño Southern Oscillation (ENSO), are expected to operate over large spatial scales, synchronizing fluctuations of disease incidence across space [i.e., the Moran effect in population dynamics (9, 10)]. A recent study has shown, however, that the spatiotemporal dynamics of cholera in Dhaka, Bangladesh, are not homogeneous at intraurban scales (11). Two regions or clusters were identified, corresponding, respectively, to the highly populated core and the more rural periphery. The urban core was shown to be more climatesensitive, acting to propagate climate perturbations in cholera infection risk to the r...